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Biomedical subjects

C Rey

Publications and source records attributed to C Rey.

At least 37 records · Page 2Linked to original sources

Signal-averaged electrocardiography in children with anthracycline-induced cardiomyopathy.

The aim of the present study was to determine if signal-averaged ECG of patients with anthracycline-induced left ventricular dysfunction could differentiate between patients with anthracycline-induced cardiotoxicity and those without. Sixteen children with anthracycline-induced cardiomyopathy, aged 6.5 to 15.5 years (anthracycline dose = 198-737 mg/m2), and 31 patients aged 5.0 to 16.7 years, who received anthracyclines without evidence of left ventricular dysfunction (anthracycline dose = 120-517 mg/m2), were studied with signal averaged ECG. The two groups were comparable in age, body surface area, and time since completion of chemotherapy. Signal averaged ECG parameters of the patients were compared with data obtained from 530 healthy children. These parameters were converted to z-scores to account for growth-related changes in signal averaged ECG recordings. Z-scores for filtered QRS duration and low amplitude terminal signal < 40 microV were significantly lower (p = 0.002 and p = 0.015, respectively), and Z-score for root mean square voltage of the last -30 ms of filtered QRS tended to be higher (p = 0.06) in patients with left ventricular dysfunction. Filtered QRS duration lower than -1.5 SD was found in 4 of 16 patients with left ventricular dysfunction and in only 1 of 31 patients without (p < 0.05) yielding a sensitivity of 25% and a specificity of 97% to detect left ventricular dysfunction. Only 1 patient had late potentials; his left ventricular function was normal. Left ventricular mass index tended to be lower in patients with left ventricular dysfunction (p = 0.07), whereas left ventricular diastolic diameter was similar in the two groups. The mechanism that accounted for the difference in signal averaged-ECG between the two groups of patients could be linked with the decrease in left ventricular mass in patients with left ventricular dysfunction. In conclusion, children with left ventricular dysfunction following anthracycline therapy have a SA ECG different from those without left ventricular dysfunction, which is mainly characterized by a lower filtered QRS duration. A prospective study is needed in order to determine if this modification of SA ECG recordings precedes alteration of left ventricular function, and, therefore, if it could help in early detection of cardiac toxicity of anthracyclines.

Adolescent↗

Phospholipids reacylation and palmitoylcoa control tumour necrosis factor-alpha sensitivity.

From the hypothesis that in TNF-alpha-resistant cells the activity of mitochondrial phospholipase A2 could be reversed by a lysophospholipid acyltransferase, we report that the mitochondrial reacylation of phosphatidylcholine as phosphatidylethanolamine was considerably higher in C6 (TNF-alpha-resistant) than in WEHI-164 (TNF-alpha-sensitive) cells. TNF-alpha did not modify the phospholipids' reacylation in C6, while in WEHI-164 it was increased several-fold. These results suggest that TNF-alpha is not sufficient to restore the barrier permeability in sensitive cells, but may be enough to explain the absence of permeability change in resistant cells. AcylCoA esters, depending on whether the acyl group is unsaturated or saturated (palmitic acid), could control membrane permeability either by participating in the reacylation of phospholipids or keeping the pore in a closed state. The analysis of the endogenous acylCoA ester pools of both cell lines show that the amount of palmitoylCoA is higher in resistant than sensitive cell lines. TNF-alpha treatment does not change these results.

Acetylation↗

Dissolution of poorly crystalline apatite crystals by osteoclasts determined on artificial thin-film apatite.

Poorly crystalline apatite (PCA) crystals introduced into bone tissue should be stable for a definite period before they are dissolved as a result of a host response. In this report, the dissolution of PCA crystals by the action of osteoclasts was studied on artificial thin films. These consisted of PCA crystals having similar crystallographic properties to bone crystals which were developed for assaying the osteoclast activity in vitro. The dissolution of minerals by osteoclasts decreased along with the decreased amount of labile phosphate and hydrogen phosphate domains of apatite crystals, which were caused by the crystal maturation temperature. A profound effect on mineral dissolution by pH in the culture medium was also shown. Low acidity considerably increased mineral dissolution, whereas a slight alkalinity totally blocked mineral dissolution. There was little difference in the mineral dissolution behavior of osteoclasts near the physiologic pH. In addition, it was determined whether mineral dissolution by osteoclasts was dependent on the destruction of the organic matrix. Nocodazole was introduced to inhibit the secretion of hydrolytic enzymes, and acetazolamide was added to inhibit acid production by the osteoclasts. There was no significant change as a result of nocodazole addition on mineral dissolution or by the addition of acetazolamide on degradation of collagen. These results indicate that small changes in the physicochemical properties of apatite crystals can decrease resorption by osteoclasts, which can be highly activated at low pH. These results also suggest that mineral dissolution and organic degradation by osteoclasts are self-regulating.

Acetazolamide↗

Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children.

OBJECTIVES: To evaluate procalcitonin (PCT) as a diagnostic marker of bacterial sepsis in critically ill neonates and children and to compare the results of PCT with those of C-reactive protein (CRP) and serum amyloid (SAA). DESIGN AND SETTING: Prospective, observational study in neonatal and pediatric intensive care units. PATIENTS: A total of 116 divided into four groups according to age and diagnosis: neonates (aged 3-30 days) with sepsis (n = 20), neonates without sepsis (n = 26), children (aged 2-12 years) with sepsis (n = 32), and children without sepsis (n = 38). INTERVENTIONS: Serum PCT, CRP, and SAA were measured on admission or when a bacterial sepsis was suspected. Area under the receiver operating characteristic (ROC) curve, optimum predictive values, and optimum diagnostic cut off values were evaluated. RESULTS: Admission PCT was significantly higher in neonates and children with sepsis than in the other groups. In the neonates the area under the ROC curve was 0.99 for PCT, 0.95 for CRP, and 0.98 for SAA; in the children it was 1 for PCT, 0.93 for CRP, and 0.96 for SAA. Cutoff concentrations for optimum prediction of sepsis in the neonates were PCT > 6.1 ng/ml (diagnostic efficiency: 93.8%), CRP > 23.0 mg/l (89.7%), and SAA > 41.3 mg/l (95.3%); in the children they were PCT > 8.1 ng/ml (100%), CRP > 22.1 mg/l (89.8%), and SAA > 67.2 mg/l (94.4%). CONCLUSION: In critically ill children PCT concentration is a better diagnostic marker of sepsis than CRP and SAA. In critically ill neonates, however, PCT, CRP, and SAA are similar diagnostic markers of sepsis. A PCT concentration higher than 8.1 ng/ml identified all children with bacterial sepsis.

Amyloid↗

Mechanisms of action and therapeutic potential of strontium in bone.

The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.

Animals↗

Usefulness of route of transmission, absolute CD8+ T-cell counts, and levels of serum tumor necrosis factor alpha as predictors of survival of HIV-1-infected patients with very low CD4 + T-cell counts.

Potential cofactors of survival in HIV-1-infected patients with CD4+ T-cell counts of < or = 100 cells/microl were investigated. All 132 patients with CD4+ T-cell counts of < or = 100 cells/microl were selected from 416 patients included in an antiretroviral therapy cohort (1989-1999). Fifty of 54 deaths were due to AIDS. There were significant associations (P<0.05) between survival and CD8+ T-cell counts, clinical AIDS stage, risk group, and antiretroviral drug regimen after baseline, but only the use of protease inhibitors had an independent effect on survival (hazard ratio [HR], 0.096; 95% confidence interval [95%CI], 0.094-0.097). A substudy restricted to the cohort of 108 patients never exposed to PIs detected independent associations between survival and CD8+ T-cell counts (P=0.0016), experience with antiretroviral therapy before baseline (HR, 2.52; 95%CI, 1.31-4.82), sexual risk group for HIV infection (HR, 3.7; 95%CI, 1.92-7.12), and levels of serum tumor necrosis factor alpha (P=0.02). This study confirms that the use of PI-containing antiretroviral regimens strongly predicts survival of HIV-1-infected patients with very low CD4+ T-cell counts. When the study was restricted to patients never exposed to PIs, the parenteral route of disease transmission, high absolute CD8 + T-cell counts, and low serum levels of tumor necrosis factor alpha were independent predictors of survival in extremely advanced HIV-1 disease.

Acquired Immunodeficiency Syndrome↗

Palmitic and stearic acids bind Ca2+ with high affinity and form nonspecific channels in black-lipid membranes. Possible relation to Ca2+-activated mitochondrial pores.

A mitochondrial hydrophobic component that forms Ca2+-induced nonspecific ion channels in black-lipid membranes (Mironova et al., 1997) has been purified and its nature elucidated. It consists of long-chain saturated fatty acids--mainly palmitic and stearic. These fatty acids, similar to the mitochondrial hydrophobic component, bind Ca2+ with high affinity in comparison with unsaturated fatty acids, saturated fatty acids with shorter aliphatic chains, phospholipids, and other lipids. Ca2+-binding is inhibited by Mg2+ but not by K+. For palmitic acid, the Kd for Ca2+ was 5 microM at pH 8.5 and 15 microM at pH 7.5, with the Bmax of 0.48 +/- 0.08 mmol/g. This corresponds to one Ca2+ ion for eight palmitic acid molecules. The data of IR spectroscopy confirm that Ca2+ does not form ionic bonds with palmitic and stearic acids under hydrophobic conditions. It has been found that in the presence of Ca2+, palmitic and stearic acids, but not unsaturated FFA induce a nonspecific permeability in black-lipid membranes. Addition of Ca2+ in order to induce the permeability transition, increases the extractable amount of palmitic and stearic acids, the effect being prevented by a phospholipase A2 inhibitor. The possible involvement of palmitic and stearic acids in the mitochondrial nonspecific permeability is discussed.

Animals↗

Adsorption of vascular endothelial growth factor to two different apatitic materials and its release.

The aim of our study was to assess the ability of calcium phosphate powders to serve as growth factor carriers. Vascular endothelial growth factor (VEGF), in particular, is locally involved in the bone formation process throughout osteoblast differentiation. Two different apatitic substrates were tested: hydroxyapatite (HA), widely used as biomaterial, and nanocrystalline carbonated apatite (CA), which has a composition similar to bone mineral crystals. These materials have been compared for their VEGF adsorption and release properties. The adsorption of the growth factor was higher on CA than on HA probably due to differences of both the proteins and the powders involved. The specific activity of the VEGF released was also tested to determine the available activity for cells in contact with these materials. Interestingly, the bioactivity of the VEGF released from CA quantified on fetal bovine aortic endothelial cells (FBAE) by evaluating the proliferation activity, exhibited no marked difference compared to native VEGF. Qualitatively, VEGF adsorbed on CA material induced well-defined collagen type I immunostaining on osteoblast cells compared to the staining obtained after VEGF adsorption on HA.

Journal Article↗

Hepatic stellate cell proliferation is an early platelet-derived growth factor-mediated cellular event in rat cholestatic liver injury.

SUMMARY: After liver injury, hepatic stellate cells (HSC) undergo a pleiotropic response termed "activation" that also occurs in culture models and ultimately leads to the conversion of HSC into myofibroblasts expressing smooth muscle alpha-actin (alpha-SMA). The onset of HSC proliferation in primary culture coincides with the induction of platelet-derived growth factor receptor-beta (PDGFR-beta) expression, while platelet-derived growth factor (PDGF) is the most potent mitogen for culture-activated HSC. Yet, the mechanisms and the stage of activation required for HSC proliferation in the intact liver are still uncertain. In the present study, we analyzed the proliferative response of HSC to rat cholestatic liver injury and the role of PDGF in this response. After in vivo incorporation of bromodeoxyuridine (BrdU), pure vitamin A-containing HSC were isolated at different time points after bile duct ligation (BDL) or sham operation and were analyzed by means of flow cytometry. The induction of HSC proliferation, as ascertained by BrdU incorporation, occurred between 24 and 48 hours and reached a plateau as soon as 48 hours after BDL. Flow cytometry and immunoblot analyses of HSC indicated that the induction of proliferation in HSC coincided with the up-regulation of PDGFR-beta protein on their surface but preceded that of alpha-SMA. A dose-dependent inhibition of PDGF-BB-induced HSC proliferation by STI571, a PDGF receptor tyrosine kinase inhibitor, was documented in vitro. Daily intraperitoneal injections of STI571 (20 mg/kg) caused a 60% reduction in BrdU positive isolated HSC and in the amount of desmin-immunoreactive sinusoidal cells on liver tissue sections in 48-hour bile duct-ligated rats. These results indicate that cholestatic liver injury elicits an early proliferative response in HSC that is mainly mediated by PDGF, and which precedes HSC phenotypic conversion into myofibroblasts.

Actins↗

Long-term follow-up of children and adolescents with syncope; predictor of syncope recurrence.

BACKGROUND: Previous studies have shown that investigation by tilt testing is very appropriate in paediatrics, but the characteristics of children and adolescents who are at high risk of recurrent syncope, once the diagnosis is established, remain unclear. This study was set up to analyse the risk factors attributed to syncope recurrence in paediatric patients. METHODS: One hundred and one children and adolescents aged 7 to 18 years, undergoing a tilt test for recurrent syncope, were studied. They were subsequently followed-up in clinic visits with a final interview at the clinic or by telephone at the end of the follow-up period. RESULTS: A head-up tilt test elicited syncope or pre-syncope in 67 children. The positive responses included vasovagal syncope in 58 patients and psychogenic syncope in nine patients. Gender, age, number of pre-tilt test syncopal episodes or duration of symptoms made no difference to children with positive or negative tilt test results. Following the tilt test, 43 of 67 children with a positive tilt test were treated empirically. No treatment was prescribed for the remaining 24 with a positive test, or for those with a negative tilt test. There were no differences between treated and untreated children with respect to the number of pre-tilt test syncopes, duration of symptoms and duration of follow-up. Follow-up data were available in 97 children. During a mean follow-up of 46+/-28 months, syncope recurred in 31 children (32%). The recurrence rate was similar between positive and negative tilt test groups (22/66 vs 9/31, respectively; P=ns), as well as between treated and untreated children (14/43 vs 8/23, respectively; P=ns). When comparing syncope-free children at follow-up in a univariate analysis, children with recurrent syncope reported a greater number of historical syncopal spells (7+/-8 vs 3+/-3, P=0.01). In addition linear correlation (r=0.6, 95% CI 0.47 to 0.72, P<0.0001) was significant between the number of historical syncope episodes and the risk of recurrent syncope. CONCLUSIONS: These findings suggest that the risk of syncope recurrence for children and adolescents with such a history is not correlated to the tilt test result or prophylactic treatment. The number of historical syncopal spells is, however, predictive.

Adolescent↗

Varicella complicated by group A streptococcal facial cellulitis.

An increase has been recently noted in the incidence of life-threatening group A beta-hemolytic streptococcal (GABHS) infections in children recovering from varicella. We report our experience with a patient who required pediatric intensive care unit admission because of a serious GABHS infection 1 week after the onset of varicella. Emergency physicians must look for this complication in patients with varicella remaining abnormally febrile and presenting unusual manifestations.

Amoxicillin↗

Spontaneous closure of congenital coronary artery fistulas.

Six cases of full spontaneous closure of congenital coronary artery fistulas, and one case of near closure, as seen by colour Doppler echocardiography, are presented. It is worth reconsidering the classical view that nearly all cases of spontaneous closure are eligible for surgical or percutaneous correction to prevent the development of significant and potentially fatal complications. As the natural course of coronary artery fistulas is still poorly defined, asymptomatic patients, especially those under 7 years old with small shunts, should be periodically followed up by echocardiography rather than be subjected to operative closure, even by catheterisation.

Coronary Disease↗

Leukemia inhibitory factor antagonizes gonadotropin induced-testosterone synthesis in cultured porcine leydig cells: sites of action.

In the present report, the action of leukemia inhibitory factor (LIF) on testicular steroid hormone formation was studied. For this purpose, the direct effects of LIF were evaluated on basal and human (h)CG-stimulated testosterone synthesis by cultured, purified Leydig cells isolated from porcine testes. LIF reduced (more than 60%) hCG-stimulated testosterone synthesis. This inhibitory effect was exerted in a dose- and time-dependent manner. The maximal and half-maximal effects were obtained with, respectively, 10 ng/ml (0.5 nM ) and 2.5 ng/ml (0.125 nM ) of LIF after a 48-h treatment of the Leydig cells. Such an effect of the cytokine was not a cytotoxic effect, because it was reversible and Leydig cells recovered most of their steroidogenic activity after the removal of LIF. Considering the sites of action of LIF in inhibiting gonadotropin-stimulated testosterone formation, it was shown that LIF significantly (P < 0.002) reduced, in a comparable range (about 60% decrease), testosterone synthesis stimulated with LH/hCG or with pharmacological agents that enhance cAMP levels (cholera toxin, forskolin, and PG E2), and testosterone synthesis stimulated with 8-bromo-cAMP. Such an observation indicates that the antigonadotropic action of the cytokine is exerted in a predominant manner at a step (or steps) located beyond cAMP formation. Furthermore, incubation of Leydig cells with 22R-hydroxycholesterol (5 microg/ml, 2 h), a cholesterol substrate derivative that does not need an assisted process to be delivered to the inner mitochondrial membrane, reversed most of the inhibitory effect of LIF on the steroid hormone formation. Such results indicate that LIF acts by reducing cholesterol substrate availability in the mitochondria. Consequently, LIF action was tested on steroidogenic acute regulatory protein and PBR (peripheral benzodiazepine receptor) shown to be potentially involved in such a cholesterol transfer. LIF reduced, in a dose- and time-dependent manner, LH/hCG-induced steroidogenic acute regulatory protein messenger RNA levels. The maximal inhibitory effect was obtained with 6.6 ng/ml of LIF after 48 h of treatment. In contrast, LIF had no effect on PBR messenger RNA expression or PBR binding. This inhibitory effect of LIF on Leydig cell steroidogenesis is probably exerted via an auto/paracrine action of the cytokine. Indeed, by immunohistochemistry, LIF and LIF receptor proteins were identified in Leydig and Sertoli cells but not in other testicular cell types, except for LIF receptor in spermatogonia. Furthermore, the presence of LIF and its receptor in Leydig cells at the neonatal and adult periods suggests that the inhibitory effect of LIF on androgen formation reported here probably occurs in both the fetal and the adult Leydig cell populations during testicular development.

Androstenedione↗

[Percutaneous closure of patent ductus arteriosus with the Amplatzer duct occluder. Results of 29 patients].

The authors report their experience of percutaneous closure of large patent ductus arteriosus with the Amplatzer duct occluder. The age of the patients ranged from 3 months to 72 years (average 24 months) with body weights of 3.9 to 74 Kg (average 16 Kg). The smallest angiographic diameter of the ductus was 4.0 +/- 1.3 mm at angiography (range 1.8 to 6 mm). The occluder was inserted under local anaesthetic with control aortography in all but one case who required general anaesthesia. In two small babies, the implantation was performed after venous puncture alone with transthoracic echocardiographic monitoring. The implantation was successful in all but one case in which there was a distensible duct. Early angiographic control showed suppression of the shunt in 61% of patients. Secondary haemolysis was observed in one case and was corrected by a second catheterisation 4 days later, with occlusion of the duct with a balloon catheter. The patients were followed up clinically, radiologically and echocardiographically. Doppler echocardiography showed absence of a residual shunt in 24 patients (86%) one month after the procedure, in 25 patients (89%) 3 months after the procedure and in 26 patients (93%) one year after the procedure. Two patients were left with mild or moderate shunts 12 and 16 months after the attempted occlusion. No cases of aortic or pulmonary obstruction were observed. The authors conclude that the Amplatzer duct occluder is a reliable device for closing large patent ductus arteriosus. It may be proposed in young symptomatic children over 4 Kg in body weight. A high rate of occlusion is obtained with a minimal risk of complications.

Adolescent↗

[Left monoplegia revealing pulmonary arteriovenous fistual in an adolescent: occclusion with an Amplatzer occluder].

A 16 year old adolescent was admitted to hospital for investigation of a transient left monoplegia. The clinical, electric and radiological examinations were all normal. Echocardiography showed no abnormality of cardiac structures or function. Contrast echocardiography was performed and showed a right-to-left shunt suggesting a pulmonary arteriovenous fistula which was confirmed at angiography. The fistula was closed at catheterisation by a detachable balloon: in a second procedure, the balloon was deflated and contrast studies showed a recurrence of the right-to-left shunt. An Amplatzer 8/6 duct occluder was implanted with excellent results and no recurrence at 3 months.

Adolescent↗