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Biomedical subjects

C Combe

Publications and source records attributed to C Combe.

At least 73 records · Page 4Linked to original sources

Improvement in lipid profiles and triglyceride removal in patients on polyamide membrane hemodialysis.

Cardiovascular morbidity and mortality in hemodialyzed patients are increased due to the frequently abnormal lipid metabolism. It has been reported that this abnormal lipid metabolism could be partially corrected by some highly permeable membranes, such as polysulfone or cellulose triacetate. We investigated the influence of 4 months of dialysis with a polyamide membrane upon the course of lipid parameters in 6 patients presenting a hypertriglyceridemia > 2 mmol/l while on bicarbonate dialysis with a cellulose membrane. Lipid parameters improved after 4 months of hemodialysis with a polyamide membrane. Serum triglyceride and cholesterol levels decreased, while HDL cholesterol and HDL levels rose significantly (p < 0.05). Apolipoprotein B decreased significantly (p < 0.05). Following heparin administration, lipoprotein lipase activity improved (p < 0.02), associated with a decrease apolipoprotein C3 (p < 0.05). The fractional clearance rate of triglycerides rose significantly (p < 0.01). The use of highly permeable polyamide membranes results in a significant improvement in lipid disturbances of dialysis patients due to an increased lipoprotein lipase activity, induced perhaps by the removal of circulating inhibitors such as apolipoprotein C3.

Apolipoproteins↗

Diagnosis of renovascular hypertension: feasibility of captopril-sensitized dynamic MR imaging and comparison with captopril scintigraphy.

OBJECTIVE: Angiotensin-converting enzyme inhibitors may decrease glomerular filtration rate when a significant renal artery stenosis is present. The purpose of this preliminary study is to evaluate the feasibility of captopril-sensitized, dynamic MR imaging of the kidney in a series of patients with a high suspicion of renovascular hypertension and to compare the results with those of captopril scintigraphy. SUBJECTS AND METHODS: Fifteen hypertensive patients with renal artery stenosis shown by angiography were studied with sequential gadolinium-enhanced MR imaging after oral administration of 50 mg of captopril, an inhibitor of angiotensin-converting enzyme. Symmetry of onset and evolution of tubular phases between the two kidneys were analyzed, and medullary signal intensity time curves were drawn for each kidney. When asymmetry between kidneys was noted, the same dynamic study was repeated 24 hr later, without captopril sensitization. All patients also underwent renal scintigraphy after administration of captopril to compare captopril-induced changes in both techniques. Three-dimensional time-of-flight MR angiography was also performed on all patients. RESULTS: MR imaging with normal and symmetric tubular phases showed that 11 patients had no impairment of glomerular filtration after administration of captopril. MR imaging showed that four had impairment of glomerular filtration: studies without captopril were symmetric (n = 2) or slightly asymmetric (n = 2), but administration of captopril induced severe functional impairment on the side of stenosis--that is, a delayed tubular phase with late corticomedullary decrease of signal intensity in the first two patients and absence of tubular phase in the other two. The results of scintigraphy were concordant in all but one case, in which the segmental distribution of filtration impairment, shown by MR imaging, was not shown by scintigraphy. The renal artery stenosis was shown by MR angiography in 10 of 15 patients (67%). CONCLUSION: Captopril-sensitized dynamic MR imaging of the kidney is feasible in patients with renovascular hypertension. However, captopril-induced changes are not present in all patients proven to have the disease. Scintigraphy provides similar results but may ignore segmental functional involvement.

Angiotensin-Converting Enzyme Inhibitors↗

[Antibiotic-induced prolonged cholestasis: suspected induction by ceftibuten].

We report on a 43-year-old female diabetic patient who was treated with ceftibuten because of Pseudomonas aeruginosa induced otitis externa. Thereafter she developed a prolonged seven-months-persisting irreversible cholestasis. Liver puncutre revealed a canalicular and hepatocellular cholestasis without liver cell necrosis or bile duct injury. After seven-months the patient died because of antibiotic-resistant Pseudomonas-septicemia.

Adult↗

[Role of phosphorus in hyperparathyroidism secondary to non-dialysed adult chronic renal insufficiency].

Secondary hyperparathyroidism (HPT II) occurs early in the course of chronic renal failure (CRF), mainly because of decreased calcitriol levels, low levels of serum calcium, retention of phosphorus, abnormal parathyroid gland function and hyperplasia, and peripheral resistance to the action of parathormone (PTH). Amongst these factors, phosphorus retention plays a crucial role in moderate and advanced CRF, by inhibiting renal calcitriol synthesis, lowering serum calcium levels and stimulating PTH secretion. In patients with mild CRF, phosphorus restriction prevents the development of HPT II by increasing renal calcitriol secretion. In patients with advanced CRF, the suppressive effect of phosphorus restriction may be obtained independent of any changes in plasma calcitriol levels, suggesting a direct effect of phosphorus on parathyroid function. Phosphorus restriction should be used in the early stages of CRF, together with a sufficient intake of calcium in the form of phosphorus chelating salts. When phosphorus and calcium serum concentrations are normalised but PTH levels are not in the target range, 1 alpha hydroxy vitamin D3 derivatives may be used, with a careful monitoring to avoid high serum levels of phosphorus or calcium.

Adult↗

Induction of intercellular adhesion molecule-1 by monocyte adhesion to endothelial cells in human culture system.

Increased monocyte adhesion to the endothelial lining of blood vessels by cytokine-inducible adhesion proteins is a crucial event in inflammatory processes. Moreover, adherence is known to induce cytokine gene expression, suggesting a possible positive feedback mechanism. Therefore, we determined whether monocyte adhesion to endothelial cells (ECs) amplifies their adhesion by inducing intercellular adhesion molecule 1 (ICAM-1), and whether such positive feedback mechanism could be mediated by secretion of interleukin-1 (IL-1). Using monocyte-EC couples obtained after monocyte adhesion to ECs, and methods of quantitative polymerase chain reaction and immunofluorescence flow cytometry, we showed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a time-dependent increase of cell surface expression of ICAM-1, mainly on ECs, and couple adhesiveness, after monocyte adhesion to ECs. Anti-ICAM-1 monoclonal antibody inhibited 63% of the enhancement of adhesiveness induced on monocyte-EC couples by previous monocyte adhesion, suggesting that monocyte adhesion to ECs induces an increase of couple adhesiveness which is partially dependent on the ICAM-1 pathway. The early ICAM-1 mRNA induction was associated with a fast induction of IL-1 beta mRNA and a 7.7-fold increase in IL-1 beta protein in supernatant. However, 30% of this 2-hour ICAM-1 mRNA peak was abolished by recombinant soluble human IL-1 receptor, suggesting that the early ICAM-1 over-expression was partially mediated by IL-1 beta, and could be induced directly by adherence. The second ICAM-1 mRNA peak was accompanied by a marked increase in IL-1 beta mRNA and protein secretion (2.6 ng/ml). The binding to ICAM-1 did not appear to directly stimulate IL-1 beta synthesis. These results indicate that monocyte adhesion to endothelial cells appears to stimulate their own recruitment via induction of ICAM-1 thereby constituting a self-perpetuating positive feedback system.

Base Sequence↗

Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice.

Mice injected with LPS (10 mu g/mouse, sc) or saline were submitted to a 15-min restraint stress and sacrificed 1 or 2 h later to assess the effect of stress on the induction of interleukin-1beta (IL-1beta) and other proinflammatory cytokines (IL-1alpha, IL-1ra, IL-6, and tumor necrosis factor-alpha) in the spleen, pituitary, hypothalamus, hippocampus, and striatum. LPS-induced cytokine gene expression, as determined by comparative RT-PCR, was lower in stressed than in nonstressed mice. LPS increased plasma and tissue levels of IL-1beta, as determined by ELISA, but this effect was less marked in stressed than in nonstressed mice. These results are discussed in relation to the modulatory effects of glucocorticoids on cytokine production.

Animals↗

USPIO-enhanced MR imaging of glycerol-induced acute renal failure in the rabbit.

Enhanced-MR imaging in combination with ultrasmall superparamagnetic iron oxide (USPIO) was used in the glycerol-induced model of acute renal failure (ARF) in the rabbit to detect renal perfusion abnormalities. A control group (n = 5) and an ARF group (n = 5) were studied after intramuscular injection of glycerol (10 ml/kg) with T2-weighted spin-echo sequence at 1.5 T and a 27 mumol/kg IV dose of iron. The signal intensity (SI) was quantified in the cortex, the outer medulla (OM), and the inner medulla (IM). In control rabbits, the maximum SI decrease after USPIO injection was in the OM (76% +/- 3.6), as this is the region of maximal vascular density, then in the IM (73.4% +/- 2.9). In the glycerol group, SI loss in the OM (61% +/- 12.6) and the IM (45.2% +/- 16.24) was significant less than in the control group (p < .05). Pathology results showed fibrinous thrombus in the efferent arterioles and congestive aspect of the vasa recta in the medulla. We argue that a reduced medullary concentration of USPIO in the renal failure group is indicative of medullary hypoperfusion.

Acute Kidney Injury↗

Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS.

To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain.

Animals↗

Evaluation of red blood cell lipoperoxidation in hemodialysed patients during erythropoietin therapy supplemented or not with iron.

To investigate the effects of erythropoietin (rHuEPO) therapy supplemented or not with iron on hemolysis in hemodialysed patients (HD) we evaluated lipoperoxidation (LPO) by assaying (i) the red blood cell (RBC) antioxidant enzymatic system including superoxide dismutase (SOD), glutathione peroxidase, and catalase (Cat), (ii) RBC polyunsaturated fatty acids (PUFA) and (iii) malondialdehyde (MDA). Group 1 included 12 HD patients, group 2 had 7 HD patients with iron supplementation, group 3 comprised 12 HD patients with rHuEPO therapy and group 4 included 9 HD patients with both iron and rHuEPO therapies. No LPO was found in group 1 as regards MDA and PUFA levels. However, SOD and Cat activities were significantly elevated as compared to controls (p < 0.001). In the second group, a significant decrease in PUFA percentage was observed, particularly in 20:4(n-6) and 22:4(n-6) (the main ones involved in LPO) as compared to the other groups, whereas total MDA level was higher than that of the other groups. Similarly a decreased SOD activity was observed as compared to group 1 (p < 0.001), indicating its inactivation subsequent to an hyperproduction of reactive oxygen species through iron injection. In groups 3 and 4 no change was observed in MDA levels or PUFA percentages indicating no LPO. However, marked differences were observed in the enzymatic defense system. Particularly in group 3, SOD and Cat activities decreased when compared to group 1 (p < 0.001) whereas the association of erythropoietin and iron (group 4) increased the three enzymatic activities (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term control of hyperparathyroidism in advanced renal failure by low-phosphorus low-protein diet supplemented with calcium (without changes in plasma calcitriol).

Phosphorus (Pi) retention linked to chronic renal failure (CRF) favors secondary hyperparathyroidism (HPT). Reduction of Pi and protein intake has been shown to prevent the development of HPT in CRF. The aim of the present study was to assess in patients with advanced CRF the long-term effects on phosphate and calcium metabolism of a low-Pi (5-7 mg/kg/day), low-protein (0.4 g/kg/day) diet providing 300 mg/day calcium (Ca) and supplemented with amino acids and ketoacids, Ca carbonate (400-800 mg/day) and vitamin D2 (1,000 IU/day). Twenty-nine patients with advanced CRF (glomerular filtration rate (GFR) 13.7 +/- 4.5 ml/min) were selected for the study, on the basis of a follow-up of a least 2 years and a satisfactory compliance to the prescribed diet. At the start of the study, biological evidence of HPT was present with increased plasma PTH concentration (144 +/- 95 pg/ml), increased plasma Pi (1.57 +/- 0.33 mmol/l), an increase in alkaline phosphatase activity and plasma osteocalcin concentration. Plasma PTH concentration was positively correlated with plasma Pi and inversely with plasma Ca concentrations and GFR. Pi and protein restriction induced a significant correction of HPT within 3 months after starting the diet. After 2 years of diet, despite the diminution of GFR (11.1 +/- 3.7 ml/min, p < 0.0001), plasma PTH was still lower than at the start of the diet (88 +/- 57 pg/ml, p < 0.01), as was plasma Pi (1.32 +/- 0.24 mmol/l, p < 0.001), total plasma Ca being higher (p < 0.01). Plasma PTH levels were correlated only to plasma Ca concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Arthritis after hepatitis B vaccination. Report of three cases.

Side effects of hepatitis vaccination are rare. Only a few cases of arthritis after hepatitis vaccination have been published. We report on three cases of vaccination-induced arthritis with different resulting disease. Two cases show the pattern of reactive arthritis. None of them was associated with HLA-B27. In the third case onset of rheumatoid arthritis was triggered by hepatitis vaccination. These three cases show that arthritis after hepatitis B vaccination probably is more common than reported so far, especially in a genetically predisposed subject (two of our patients expressed HLA-DR4).

Adolescent↗

Correction of chronic metabolic acidosis in haemodialysed patients by acetate-free biofiltration does not influence parathyroid function.

In eight patients remaining acidotic after more than 1 year of bicarbonate haemodialysis, we studied the effect of correcting the chronic metabolic acidosis using acetate-free biofiltration for 4 months on the course of secondary hyperparathyroidism. An AN69 capillary membrane was employed with a bicarbonate infusion rate initially set at 1.8 l/h in all patients and then adjusted in each one to obtain a predialysis bicarbonate of > or = 23 mmol/l. Standard blood chemistry parameters were determined every 2 weeks. Measurements of PTH, calcifediol and calcitriol, as well as calcium-PTH curves were determined at the beginning and end of the study. While acetate-free biofiltration appears to be an adequate technique for the correction of chronic metabolic acidosis when bicarbonate dialysis fails, this study indicates that it does not influence secondary hyperparathyroidism in haemodialysed patients. The level of intact PTH did not vary significantly and the calcium-PTH curves at 0 and 4 months were superimposable with no significant differences in the set point and the slope of the curves.

Acidosis↗

[Nutrition and continuous ambulatory dialysis].

Nearly 50% of patients treated by CAPD develop a more or less severe state of denutrition with which morbidity and mortality are closely linked. Though many biological and biophysical examinations have been proposed to evaluate the nutritional status of patients, it appears that, from a practical standpoint, the information furnished by the medical history, anthropometric parameters, nitrogen balance and serum protein levels are sufficient. The prevention and/or treatment of this malnutrition can only be achieved by correcting the two principal contributing factors which are the reduced energetico protidic supply (especially protidic) and the inadequate dialysis in connection particularly with the progressive loss of the residual renal function.

Blood Proteins↗

One-year enzyme-linked immunosorbent assay follow-up of human interleukin for Da cells/leukemia inhibitory factor in blood and urine of 22 kidney transplant recipients.

The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia.

Adolescent↗

Granulocyte activation and adhesion molecules during hemodialysis with cuprophane and a high-flux biocompatible membrane.

Hemodialysis with complement-activating membranes, such as cuprophane, induces neutropenia and expression of the granulocyte adhesion receptor Mac-1 (CD11b/CD18), while hemodialysis with noncomplement-activating membranes does not. Increased expression of CD11b by neutrophils may mediate cuprophane-induced leukopenia. However, the rebound granulocytosis that follows leukopenia is not fully understood. Ten patients on regular hemodialysis were included in a cross-over study. Hemodialysis was performed for 2 weeks with cuprophane and 2 weeks with polyamide, a high-flux noncomplement-activating membrane. At the end of each period, the following parameters were determined during a hemodialysis session: C5a concentration by enzyme immunoassay and the neutrophil expression of CD11b, LFA-1 (CD11a/CD18), and the antigen recognized by MoF11 (MoF11 Ag), a monoclonal antibody that recognizes activated neutrophils, by immunofluorescence flow cytometry. Hemodialysis with cuprophane induced an increase in C5a concentration and in the expression of CD11b and MoF11 Ag, which were maximal after 15 minutes of hemodialysis, at the nadir of neutropenia. CD11b expression was maintained throughout hemodialysis, despite the reversal of neutropenia. Conversely, after peak expression, C5a and MoF11 Ag decreased as the neutrophil count increased to baseline values. Polyamide hemodialysis did not induce variations in C5a concentration, nor in CD11b and MoF11 Ag expression. CD11a/CD18 expression remained stable during hemodialysis with both membrane types. Neutrophil activation, as determined by MoF11 Ag expression, was correlated with the evolution of neutrophil count and C5a concentration during cuprophane hemodialysis, while CD11b expression was not correlated with neutrophil count throughout dialysis. A decrease in neutrophil activation could explain in part the detachment of neutrophils previously bound to endothelium and, therefore, the reversal of neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphorus and protein restriction and parathyroid function in chronic renal failure.

Phosphorus retention as a result of chronic renal failure (CRF) induces secondary hyperparathyroidism (HPT II) while supplemented low-phosphorus low-protein diets (LPD) prevent it. The aim of this study was to assess in seven patients with advanced CRF and biological HPT II the effects of a LPD providing daily 5 to 7 mg/kg phosphorus, 0.4 g/kg protein, 300 mg calcium (Ca) and supplemented with amino acids, ketoacids, CaCO3 and vitamin D2, on the relationship between ionized Ca (iCa) and PTH concentrations. Hyper- and hypocalcemia were induced by CaCl2 and Na2-EDTA infusion. After three months of LPD, serum phosphorus decreased from 1.59 +/- 0.15 to 1.26 +/- 0.24 mmol/liter (mean +/- SEM, P < 0.02), basal PTH levels from 251 +/- 25 to 127 +/- 16 pg/ml (P < 0.03), while basal iCa and GFR did not vary. The sigmoidal PTH-calcium curve shifted downward with maximal PTH decreased from 482 +/- 86 to 319 +/- 60 pg/ml (P < 0.02) and minimal PTH from 35 +/- 4 to 21 +/- 4 pg/ml (P < 0.05). On the other hand, the slope of the % maximal PTH-iCa curve, which is an indicator of the sensitivity of the parathyroid cell to changes in iCa concentrations, did not vary significantly. The set point of Ca and calcitriol levels were not modified. These results demonstrate a direct inhibition of PTH secretion over a wide range of iCa concentration by LPD in patients with advanced CRF and mild HPT II over a three months period. This effect is independent of changes in plasma calcitriol levels.

Adult↗

Effects of a low-protein, low-phosphorus diet on metabolic insulin clearance in patients with chronic renal failure.

The metabolic clearance rate (MCR) of insulin was studied in 17 nondiabetic patients with advanced chronic renal failure (creatinine 479 +/- 15 mumol/L, glomerular filtration rate 14.6 +/- 2.9 mL/min) before and after 3 mo of a low-protein, low-phosphorus diet (LPD) providing daily per kilogram 0.3 protein of vegetal origin and 3-5 mg inorganic phosphorus. The energy supply (146 kJ.kg-1 x d-1) was furnished mainly by carbohydrates. The diet was supplemented with a mixture of essential amino acids and keto-analogues. The MCR of insulin was determined by using the euglycemic clamp technique. Before the diet the MCR of insulin was low (450 +/- 127 mL.min-1 x m-2) but increased significantly at the third month (568.8 +/- 148 mL.min-1 x m-2), reaching values close to the MCR of control subjects (630 +/- 135 mL.min-1 x m-2). Identical results have been described during hemodialysis of anephric patients, leading us to hypothesize that an LPD reduces the production of dialyzable factors that interfere with peripheral insulin metabolism.

Adult↗

Evaluation of intrarenal distribution of ultrasmall superparamagnetic iron oxide particles by magnetic resonance imaging and modification by furosemide and water restriction.

RATIONALE AND OBJECTIVES: The steady-state intrarenal distribution of ultrasmall superparamagnetic iron oxide (USPIO) particles in the cortex, the outer medulla (OM), and the inner medulla (IM) was investigated using magnetic resonance imaging in the normal rabbit kidney and in situations that modify the corticopapillary osmotic gradient. METHODS: Experiments were performed on rabbit kidneys with T2-weighed spin-echo sequence and T2-weighted gradient-recalled-echo sequence. The intravenous dose was 27 mumole/kg of iron in all rabbits. Three groups were studied: normally hydrated rabbits (n = 5), after water restriction (n = 5) to increase the osmotic gradient, and after furosemide injection (n = 5) to decrease the osmotic gradient. The signal intensity (SI) was quantified by region of interest placed on the cortex, the OM and the IM. RESULTS: In normally hydrated rabbits, a maximal decrease of the SI after USPIO was noted in the medulla, without significant difference between the OM and the IM on spin-echo sequences. The decrease of the SI was maximal in the IM on gradient-recalled echo sequences. In dehydrated animals, the maximum SI loss was in the OM. The furosemide-induced transient enhancement of the IM lasted a few minutes. CONCLUSIONS: The observed SI changes due to the distribution of the USPIO between OM and IM were not based on modifications of the osmotic gradient. The authors suggest that these SI changes were mostly dependent on the vascular density.

Animals↗