Search PubMed⌕ Search

Biomedical subjects

C Combe

Publications and source records attributed to C Combe.

At least 37 records · Page 2Linked to original sources

Procalcitonin: a new marker of inflammation in haemodialysis patients?

BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in dialysis patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months, 12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25 patients and low-flux in 37 patients, without reuse). PCT levels were compared with other markers of inflammation and nutritional status, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine, albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb), and epoetin (Epo) doses. Patients were divided into different groups according to their infectious and vascular status. RESULTS: PCT plasma levels before dialysis were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients with a current infection, while IL-6 values were elevated in all patients regardless of infection status. Plasma CRP concentrations before dialysis were 21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other and were all negatively correlated with albumin. Prealbumin was negatively correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin was negatively correlated with IL-6 and Epo doses, while Epo doses were positively correlated with IL-6 but not with CRP or PCT. The 23 patients with both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and prealbumin concentrations, and the highest fibrinogen concentrations and Epo doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with currently used markers of inflammation such as CRP and fibrinogen, and negatively correlated with markers of nutritional status such as albumin. The concomitant elevations in PCT and CRP could be more sensitive in the evaluation of inflammation than each marker separately.

Aged↗

Determinants of arterial compliance in patients treated by hemodialysis.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality among hemodialysis patients. Several studies have demonstrated the importance of a reduction in arterial compliance in the development of cardiovascular complications, reflecting the interaction of functional and structural alterations of the peripheral arterial system and left ventricle. The aim of the present study was to demonstrate that arterial compliance, evaluated by automated recording of the QKd interval, was lower in hemodialysis patients than in normal subjects. A secondary objective of the study was to assess the influence of several factors, including calcium-phosphorus parameters, on decreased arterial compliance in these patients. PATIENTS AND METHODS: Arterial compliance was evaluated in 24 chronic hemodialysis patients who had normal (n = 12) or high blood pressure (n = 12), using a method of measuring systolic wave velocity by automated recording of the QKd interval. This interval corresponds to the time (in ms) between the onset of the electrocardiogram QRS complex (Q) and the Korotkoff (K) sound at diastolic pressure (d) heard over the brachial artery during blood pressure measurement. The analysis was performed in comparison with reference values obtained in a population with normal renal function. The other parameters determined were: age, duration of chronic renal failure, duration of hemodialysis therapy, left ventricular mass, vascular calcification score, serum total and ionized calcium, phosphorus, parathyroid hormone, calcidiol, calcitriol, and blood concentration of hemoglobin. RESULTS: The arterial stiffness of all the patients was increased significantly (p < 0.001) compared to reference values obtained from subjects without renal failure, the average age, height, and blood pressure of whom were similar to those of the patients. Multivariate analysis demonstrated a positive relationship among the QKd interval, serum total calcium, and the duration of hemodialysis. This suggested that arterial wall elastic properties were dependent not only on hypertension and constraints of pressure, but that they were also influenced by calcium and phosphorus metabolism and the duration of renal substitution therapy. CONCLUSIONS: Arterial compliance, evaluated by the ambulatory method of QKd measurement, is reduced in chronic hemodialysis patients, and is inversely correlated with serum calcium concentration and dependent on the previous duration of hemodialysis therapy.

Adult↗

[Dialysis Outcomes and Practice Patterns Study: data on the use of central venous catheters in chronic hemodialysis].

Central venous catheters are widely used as vascular accesses for chronic haemodialysis. Different factors may lead to catheter use, whether clinical such as emergency dialysis, or related to practices specific to each dialysis unit or country. The Dialysis Outcomes and Practice Patterns Study is an observational study of more than 10,000 representative patients treated by haemodialysis followed over a two-year period in the United States, Japan, and in five European countries (France, Germany, Italy, Spain, United Kingdom). DOPPS data from the United States and Europe about catheters are reported in this paper. Catheter use is less frequent in Europe than in the US, both in incident and prevalent patients, and in patients who have been seen by a nephrologist in the pre-dialysis period. Tunneled and untunneled catheters are each associated with a significantly higher frequency of access infection compared to native arteriovenous fistulae and grafts. Patients with important comorbidities such as diabetes, cardiovascular diseases, malnutrition or dementia are more likely to be dialysed with tunneled catheters. Furthermore, patients initiating hemodialysis with a tunneled catheter display higher mortality risk compared to patients starting hemodialysis with a permanent access. In summary, DOPPS data indicate that central venous catheters are used for chronic haemodialysis in patients with a high level of morbidity, and that their utilisation is associated to an additional risk, particularly of infection, and to a lower survival for tunneled catheters. Appropriate care should limit the utilisation of central venous catheters to clinically undisputable indications.

Catheterization, Central Venous↗

[Serotonin syndrome during fluoxetine poisoning in a patient taking moclobemide].

PURPOSE: To present a case of delayed serotonin syndome (SS), a less well-known adverse effect of fluoxetine intoxication. CLINICAL PRESENTATION: A 21-yr-old woman was admitted following voluntary intoxication with fluoxetine and benzodiazepines. At the time of admission, she was slightly drowsy and hypotonic but, eight hours later, she developed severe hypertonic coma despite blood concentrations of fluoxetine within the therapeutic range. Repeated toxicological analyses revealed the presence of moclobemide at non-measurable concentrations, suggesting earlier ingestion of this monoamine oxydase inhibitor. Having excluded all other likely causes of the neurological syndrome observed, a SS was postulated. Treatment was symptomatic with mechanical ventilation, sedation with thiopental and fentanyl, and neuromuscular block with pancuronium bromide. The patient recovered spontaneously 20 hr later. CONCLUSION: Physicians managing patients presenting with fluoxetine intoxication must be aware of the potential risk of SS. Treatment is symptomatic, but SS may be severe and require vital support in the intensive care environment. Review of published reports does not allow the authors to recommend a specific anesthetic management.

Adult↗

[Multi-recurrent cardiac arrest: when to discontinue cardiopulmonary resuscitation?].

A 52-year-old man developed an out-of-hospital cardiac arrest complicating a myocardial infarction. After prolonged cardiopulmonary resuscitation, he was admitted to an intensive care unit, where 25 episodes of cardiac arrests occurred within a few hours. Finally the outcome was favourable. This case raises the question of the duration a cardiopulmonary resuscitation in case of out-of-hospital and in-hospital cardiac arrest. The question is to determine how long resuscitation efforts must be prolonged after recurrent cardiac arrests.

Anti-Arrhythmia Agents↗

No change of hyperleptinemia despite a decrease in insulin concentration in patients with chronic renal failure on a supplemented very low protein diet.

Chronic renal failure (CRF) is often accompanied by hyperleptinemia caused by deficient renal metabolism of leptin and possibly increased leptin production, which in turn may result from the hyperinsulinemia and increased proinflammatory cytokine levels in patients with CRF. The hyperinsulinemia and insulin resistance observed in patients with CRF improve on supplemented very low protein diets (SVLPDs). The goal of our study is to determine whether the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is accompanied by improvement in hyperleptinemia. Thirteen patients were studied before and 1 year after following SVLPDs providing 0.3 g/kg/d of protein, supplemented with amino acids and ketoanalogues. After 1 year, patients showed markedly less hyperinsulinemia (7.4 +/- 1.6 versus 13.8 +/- 2 microU/mL at the start of diet; P: = 0.05) and insulin resistance, whereas serum leptin levels remained unchanged (16.1 +/- 4.7 versus 19.1 +/- 7.4 ng/mL at start of the study; P: = not significant). The initial correlation between serum leptin level and percentage of body fat persisted during follow-up. No correlation was found between insulin and leptin levels or between the variation of these two parameters during the study. Our study shows that the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is not accompanied by improvement in hyperleptinemia, which consequently does not appear to result from changes in carbohydrate metabolism.

Dietary Proteins↗

Nephrotoxic nephritis and obstructive nephropathy: evaluation with MR imaging enhanced with ultrasmall superparamagnetic iron oxide-preliminary findings in a rat model.

PURPOSE: To evaluate the role of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation and differentiation of different types of nephropathies. MATERIALS AND METHODS: Two experimental rat models of nephropathies were studied: a model of nephrotoxic nephritis induced by means of intravenous injection of sheep anti-rat glomerular basement membrane serum (n = 43) and a model of obstructive nephropathy (n = 6). Imaging sessions were performed with a spectrometer operating at 4.7 T with fast low-angle shot, or FLASH, sequences. Signal intensity was measured in each kidney compartment before and 24 hours after intravenous injection of USPIO (90 micromol of iron per kilogram of body weight). MR findings were compared with histologic data and urine protein levels. RESULTS: In the nephrotoxic nephritis model 24 hours after injection of USPIO, a significant signal intensity decrease (P: <.05) was present only in the cortex where the glomerular lesions were located. In the obstructive nephropathy model, the signal intensity decrease (P: <.05) was located in all kidney compartments in response to diffuse interstitial lesions. The decrease in signal intensity was due to iron uptake by either macrophages or mesangial cells gaining endocytic activity and was correlated, in the nephrotoxic nephritis model, to the degree of proteinuria. CONCLUSION: Twenty-four-hour delayed USPIO-enhanced MR imaging may help identify and differentiate various types of nephropathies.

Animals↗

Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

Analysis of Variance↗

[Upper extremity deep venous thrombosis. 40 hospitalized patients].

Deep venous thrombosis is 50 times less frequent in upper than in lower limbs. Data remain poor in the literature. Forty consecutive patients (24 males, 16 females, mean age: 54.5 years) were retrospectively analysed from 161 subjects who underwent venous explorations of the upper extremity for a 3.5 year period in the same center. Diagnosis of thrombosis was made by duplex ultrasonography (n =37) or phlebography (n =3). Main clinical manifestations were edema (n =36) and pain (n =29). Location of thrombosis was humeral (n =1), axillary (n =2), or sub-clavian (n =37, 2 bilateral). The majority of thrombosis (n =29) were secondary to cancer and venous catheter (n =19, 15 implanted ports), to central catheter alone (n =3) or cancer alone (n =7). The 11 others were associated with thoracic outlet syndrome (n =6) or apparent primary thrombosis (n =5). Thrombophilia was identified in 6 out of these 11. During follow up [mean of 9 months (0,5-36)], two patients developed pulmonary embolism, 14 a post-thrombotic syndrome and 16 patients died. Initial therapy included heparin (n =36) or fibrinolysis (n =4). Upper extremity deep venous thrombosis are mostly associated with cancers and venous catheters. Thrombophilia is frequent in the other cases. Heparin followed by oral anticoagulation is the optimal therapy whose duration depends upon underlying condition. Fibrinolysis has not been useful for preventing post-thrombotic syndrome in our study.

Adult↗

Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice.

Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.

Animals↗

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.

Animals↗

Outcome of nutritional status and body composition of uremic patients on a very low protein diet.

Concern has been raised about the nutritional adequacy of a very low protein diet (VLPD). Monthly clinical evaluation by a physician and dietitian and quarterly dietary records, anthropometric measurements, blood testing, and dual energy X-ray absorptiometry (DEXA) were used to assess the course of nutritional status for 1 year in 10 clinically stable patients (six men, four women; age, 57.1 +/- 9.3 years) with advanced chronic renal failure (mean glomerular filtration rate, 13.2 +/- 4.8 mL/min/1.73 m(2)). These patients received a VLPD providing 0.3 g/kg/d of protein and were supplemented with amino acids and ketoanalogues. Conventional nutritional markers remained unchanged after 1 year of the VLPD. However, during the same period, whole-body DEXA showed a significant decrease in lean tissue from 46.2 +/- 10.2 to 45.0 +/- 9. 8 kg (P < 0.02); limb-trunk lean tissue ratio was reduced from 0.86 +/- 0.12 to 0.82 +/- 0.12 (P < 0.02), total-body fat increased from 20.0 +/- 6.9 to 21.4 +/- 7.0 kg (P < 0.05), and the percentage of total-body fat increased from 29.2% +/- 8.7% to 31.7% +/- 8.8% (P < 0.03). These different modifications occurred abruptly during the first 3 months, then stabilized or slightly improved thereafter. These mild changes do not appear to be deleterious given the favorable long-term outcome of these patients, even after they began treatment by dialysis or after renal transplantation.

Absorptiometry, Photon↗

MPO-ANCA-Positive crescentic glomerulonephritis: a distinct entity of scleroderma renal disease?

Scleroderma renal crisis is characterized by intimal thickening of the afferent glomerular arterioles resulting in hypertension and fibrinoid necrosis of the capillary tuff. We report a 67-year-old man with long-standing systemic sclerosis who developed normotensive progressive renal failure, proteinuria, and a nephritic urinary sediment with serum myeloperoxidase-antineutrophil cytoplasmatic antibodies (MPO-ANCA). Renal biopsy showed pauci-immune crescentic glomerulonephritis but none of the typical vascular changes of scleroderma renal crisis. Because comparable cases have recently been reported from Japan, normotensive MPO-ANCA-positive crescentic glomerulonephritis may form an entity of progressive renal failure in scleroderma.

Aged↗

Thymoma associated with myasthenia gravis and minimal lesion nephrotic syndrome.

A nephrotic syndrome has been observed rarely in association with thymoma. In most of the reported cases, it occurs when the thymoma is in remission; histological examination generally shows minimal change disease. We report a case of a 43-year-old man presenting with minimal lesion nephrotic syndrome at the time of the diagnosis of thymoma and myasthenia gravis, which persists despite remission of the thymoma. The role of a disorder of T-cell function and of circulating cytokines is discussed.

Adult↗

[Effect of inhaled nitric oxide in a patient with intracranial hypertension].

Inhaled nitric oxide (NO) may be beneficial in patients with acute respiratory distress syndrome (ARDS). The effects of inhaled NO on intracranial pressure have not yet been assessed. This case shows the beneficial effects of inhaled NO in a patient with ARDS and intracranial hypertension.

Administration, Inhalation↗

Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins.

BACKGROUND: Chronic interstitial scarring contributes to the progression of renal failure in glomerular disease but its cause is unknown. The development of proteinuria could stimulate tubular cells to release cytokines, chemoattractants and matrix proteins into the interstitium, thus contributing to interstitial disease. METHODS: Polarized human tubular epithelial cells were grown on permeable supports and exposed to serum proteins on their apical surface. The release of tumour necrosis factor alpha(TNFalpha), platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) by the cells was measured using immunoassays. RESULTS: Under control conditions there was polarized release of PDGF-AB with predominant basolateral secretion (basolateral to apical ratio 4.7+/-1.6). MCP-1 release was less polarized (ratio 1. 7+/-0.5). TNFalpha was not detected. Exposure of the cells to normal human serum proteins on their apical side increased basolateral release of PDGF-AB (1.7+/-0.4 fold) and MCP-1 (2.4+/-0.2 fold). Fractionation of the serum showed that this effect on human tubular epithelial cells was reproduced by a fraction of molecular weight 40-100 kDa. The predominant proteins in this fraction were albumin and transferrin but these purified proteins alone did not alter secretion of PDGF-AB or MCP-1. CONCLUSION: This data demonstrates that human tubular cells exposed to proteins, which would be filtered in glomerular disease, produce inflammatory mediators with the potential to stimulate inflammation and scarring in the interstitium of the kidney.

Blood Proteins↗

Bone mass and dynamic parathyroid function according to bone histology in nondialyzed uremic patients after long-term protein and phosphorus restriction.

One year of a very low protein diet (VLPD) can reverse secondary hyperparathyroidism in uremic patients. We studied bone histology, bone mineral density (BMD), and dynamic parathyroid function (calcium/PTH curves) in 16 nondialyzed patients with advanced renal failure who had been receiving a VLPD for a mean of 5 yr (mean protein intake, 0.34 +/- 0.12 mg/kg x day; mean phosphorus intake, 8.2 +/- 2.1 mg/kg x day) and daily supplementation with essential amino acids and their ketoanalogs (1000 IU vitamin D2 and 1-2 g calcium carbonate). Three patients exhibited a high bone formation rate (BFR), 7 patients had normal bone remodeling, and 6 patients had a low BFR, including 2 with osteomalacia and 4 with adynamic bone disease without aluminum overload. A longer diet duration and lower caloric intake were associated with low BFR. More than half of the patients exhibited moderate or severe osteoporosis at the appendicular skeleton. The t score of femur BMD explained 65% of the BFR variance. Patients with a low BFR had a dynamic parathyroid function similar to that of patients with a normal BFR, except they had a lower capacity to buffer a calcium load, whereas patients with a high BFR had a higher basal PTH/maximum PTH and a steeper calcium/PTH curve slope; the calcium set-point was identical in the three groups.

Adult↗