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E Vidal

Publications and source records attributed to E Vidal.

At least 37 records · Page 2Linked to original sources
PubMed2004

New concepts in cyclosporine pharmacokinetic and dynamic monitoring: the impact of concomitant immunosuppression on target C2 concentrations.

BACKGROUND: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. AIM: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C2 and clarify the impact of concomitant immunosuppression. METHODS: Thirty-eight stable renal transplant recipients were treated with CsA (n=20) or CsA+MMF (n=18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. RESULTS: There were no significant differences in median CsA C2 values and CNa between the CsA alone and the CsA+MMF groups (388 microg/L and 497.5 microg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P<.001). The correlations (r) between C2 and CNa 2h were: CsA r=0.74; CsA+MMF r=0.84 (P<.001 in both cases). CONCLUSIONS: In stable renal transplant patients, median CsA C2 values below 500 microg/L were associated with inhibition of CNa and IL-2 synthesis. CNa and IL-2 production may be good biological markers of CsA immunosuppression. The measurement of CNa depends mainly on CsA concentration, whereas in vitro IL-2 production reflects the effect of both CsA and MMF. Further studies are necessary to define the optimal C2 target concentration and the possible impact of concomitant immunosuppression.

Calcineurin Inhibitors↗
PubMed2003

[Dysmetabolic hepatosiderosis, characteristics in 51 patients].

OBJECTIVE: Dysmetabolic hepatosiderosis is a recently described entity, which reunites iron overloads associated with polymetabolic syndromes, steatosis and steato-hepatitis. The aim of this study was to specify the relationship between iron overload, polymetabolic syndrome, HFE mutations of primary hemochromatosis and steatosis. METHOD: This was a 5-year retrospective study of 51 patients hospitalised and/or seen in consultation, non-alcoholic, presenting with hyperferritinemia associated with a polymetabolic syndrome and/or hepatic steatosis. RESULTS: Patients mean age was of 53 +/- 12 years with a sex ratio M/F of 5.4. Metabolic disorders were found in 97% of the non-steatosis patients (overweight: 40%, perturbed sugar metabolism: 47%, dyslipidemia: 79.5%). Hyperferritinemia was constant but moderate (513.4 +/- 280.3 ng/ml). Transferrin saturation was predominantly normal (0.44 +/- 0.17). The hepatic enzymes were normal or only slightly perturbed. Steatosis was revealed by sonography in 62% of cases. The hepatic iron overload, documented in 6 patients by hepatic needle biopsy, was discreet (concentration/age ratio of 1.64 +/- 0.19). Among the 59% patients screened for the HFE gene, 40% were positive for C282Y and/or H63D. There was no correlation between ferritin levels and iron parameters, polymetabolic syndrome parameters and hepatic enzymes. The HFE mutations had no influence on the iron parameters. CONCLUSION: Dysmetabolic hepatosiderosis must be know by hospital practitioners because of their prevalence in cases of hyperferritinemia and their therapeutic incidence.

Adult↗
PubMed2003

Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C(2).

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Area Under Curve↗
PubMed2003

Abnormal neuronal expression of the calcium-binding proteins, parvalbumin and calbindin D-28k, in aged dogs.

Disturbances of the gamma-aminobutyric acid (GABA) neurotransmitter system have been implicated in chronic degenerative neurological disease. Cognitive dysfunction and neuron loss are features in older dogs. GABAergic neurons also show immunoreactivity for specific calcium-binding proteins. Immunohistochemistry was used to study the neuronal expression of calbindin D-28k and parvalbumin in different areas of the brain in 13 dogs, aged between 2 and 13.5 years. Calbindin expression was found only in the cerebellum. There were significant differences in the quantity and distribution of neurons expressing these proteins between geriatric and adult brains. Parvalbumin- and calbindin-expressing neurons are relatively sensitive to degeneration in the cerebellum of older dogs. Parvalbumin labelling was associated with dystrophic structures that are commonly associated with ageing.

Aging↗
PubMed2002

Abnormal synaptic protein expression and cell death in murine scrapie.

Reduced expression of synaptophysin p38, synaptic-associated protein of molecular weight 25,000 (SNAP-25), syntaxin-1, synapsin-1, and alpha- and beta-synuclein, matching the distribution of spongiform degeneration, was found in the neurological phase of scrapie-infected mice. In addition, synaptophysin and SNAP-25 were accumulated in isolated neurons, mainly in the thalamus, midbrain and pons, and granular deposits of alpha- and beta-synuclein were present in the neuropil of the same areas. No modifications in the steady state levels of Bcl-2, Bax, Fas and Fas ligand were observed following infection. Yet antibodies against the c-Jun N-terminal peptide, which cross-react with products emerging after caspase-mediate proteolysis, recognize coarse granular deposits in the cytoplasm of reactive microglia. In situ end-labeling of nuclear DNA fragmentation showed positive nuclei with extreme chromatin condensation in the thalamus, pons, hippocampus and, in particular, the granular layer of the cerebellum. More importantly, expression of cleaved caspase-3, a major executioner of apoptosis, was seen in a few cells in the same regions, thus indicating that cell death by apoptosis in scrapie-infected mice is associated with caspase-3 activation. The present findings support the concept that synaptic pathology is a major substrate of neurological impairment and that caspase-3 activation may play a pivotal role in apoptosis in experimental scrapie. However, there is no correlation between decreased synaptic protein expression and caspase-3-associated apoptosis, which suggests that in addition to abnormal prion protein deposition, there may be other factors that distinctively influence synaptic vulnerability and cell death in murine scrapie.

Animals↗
PubMed2002

[Systemic lupus erythematosus and herpes virus infection: three new observations].

INTRODUCTION: Systemic lupus erythematosus is still of unknown origin. Viruses have long been postulated to play a role in its pathogenesis particularly cytomegalovirus and Epstein-Barr virus. EXEGESE: We describe three patients who presented acute onset of systémic lupus erythematosus concurrently with recent viral infection (two with cytomegalovirus and one with Epstein-Barr virus). CONCLUSION: The peculiar clinical events emphasize the difficulty of diagnosis at the onset of the disease and suggest possible role of these viruses in the pathogenesis of SLE.

Adult↗
PubMed2001

Fluorescent monitoring of kinase activity in real time: development of a robust fluorescence-based assay for Abl tyrosine kinase activity.

Fluorescent biosensors hold great promise for drug discovery. Using a solid-phase version of protein semi-synthesis, we incorporated two fluorophores at specific sites within a truncated version of the c-Crk-II protein. The resulting fluorescent protein biosensor permits the real-time monitoring of Abl kinase activity and provides a robust and rapid method for assaying Abl kinase inhibitors.

Amino Acid Sequence↗
PubMed2001

Risk factors for visual loss in giant cell (temporal) arteritis: a prospective study of 174 patients.

OBJECTIVE: To determine the risk factors--especially the effects of thrombocytosis--for permanent visual loss in patients with temporal arteritis. METHODS: One hundred seventy-four patients with temporal arteritis (147 biopsy proven) were prospectively observed for the development of permanent visual loss. We used multivariate logistic regression analysis to determine which of 17 pretreatment characteristics were associated with visual loss. RESULTS: Visual ischemic manifestations occurred in 48 (28%) patients, including permanent visual loss in 23 (13%) patients. The independent predictors associated with an increased risk of permanent visual loss were a history of transient visual ischemic symptoms (odds ratio [OR] = 6.3; 95% confidence interval [CI]: 1.4 to 29; P = 0.02) and a higher platelet count (OR = 3.7 per SD; 95% CI: 1.8 to 7.9; P = 0.001). The presence of constitutional symptoms (OR = 0.14; 95% CI: 0.02 to 0.77, P = 0.01), polymyalgia rheumatica (OR = 0.04; 95% CI: 0.01 to 0.48, P = 0.02), and C-reactive protein level (OR = 0.35 per SD; 95% CI: 0.13 to 0.92, P = 0.03) were associated with a reduced risk. Upper limb artery involvement was excluded from the multivariate model, as no patients with that problem developed permanent visual loss. Of the 87 patients who presented with thrombocytosis (platelet count >400 x 10(9)/L), 32 (37%) developed ischemic visual symptoms, compared with 16 (18%) of those without thrombocytosis. CONCLUSIONS: An elevated platelet count is a risk factor for permanent visual loss in temporal arteritis. The finding of thrombocytosis in a patient with suspected temporal arteritis should emphasize the need for urgent treatment, with consideration of using inhibitors of platelet aggregation or anticoagulation therapy.

Aged↗
PubMed2001

[Dry mouth].

The sensation of dry mouth is a common problem, often neglected. The decrease of salivary flow causes chronic oral discomfort and functional problems and predisposes to rampant dental caries and oral candidiasis. Various methods are described to evaluate salivary gland hypofunction but no single test has sufficiently high specificity and sensitivity. Categorised questionnaires and unstimulated whole saliva flow are valuable. The causes of xerostomia are numerous, of which the principal are, drug or radiation induced xerostomia and primary an secondary Sjögren's syndrome. Treatment calls for good hydration, optimal oral hygiene and prophylaxis of candidosis. All unnecessary medications must be avoided. Oral pilocarpine is the only drug which had demonstrated beneficial effects if no contraindications exist.

Candidiasis, Oral↗
PubMed2001

[Risk factors for irreversible cerebral ischemia complications from Horton's disease: prospective study of 178 patients].

PURPOSE: To search for risk factors of developing irreversible cranial ischemic complications (ICIC) in patients with giant cell arteritis (GCA) and to explore whether two subsets of patients (high risk and low risk of developing ICIC) can be defined. METHODS: One-hundred seventy-eight consecutive patients with temporal arteritis (149 biopsy-proven) were diagnosed and followed up in a department of Internal Medicine between 1976 and 1999. The patients were separated into two groups, according to the presence or absence of ICIC, with comparison of 17 clinical and biological parameters prospectively recorded for each patient using a pre-established comprehensive questionnaire. RESULTS: ICIC occurred in 25 patients (14%), with amaurosis in 22 cases. Suggestive symptoms and/or signs of temporal arteritis were present in 92% of the patients, lasting 50 days (median) before the onset of ICIC. Forty-three patients (24%) complained of transient visual ischemic symptoms (TVIS), which preceded acute blindness in 11 cases. A multivariate logistic regression, from which 28 cases with upper limb artery involvement were excluded for technical reasons (no CCII in any case, thus predicting perfectly the lack of ischemic risk, P = 0.02), indicated that the only independent variables associated with the ischemic risk were: a history of TVIS (P = 0.05), the lack of signs of polymyalgia rheumatica (PMR; P = 0.02), lower blood levels of fibrinogen (P = 0.024) and higher mean blood platelets levels (P = 0.006). However, these five variables predicted only 30% of the variability of the model. Sensitivity, specificity, positive and negative predictive values of the model reached respectively 36, 96, 64 and 88%. Overall, 86% of the cases were correctly classified with respect to the ischemic risk. CONCLUSION: The rate of ICIC should be reduced by an earlier recognition of the usual signs of temporal arteritis. Several independent risk factors of ICIC have been identified. However, the logistic model failed to predict accurately the ischemic risk in 14% of the cases, indicating that as yet unrecognised factors probably exist that play a role in the occurrence of ICIC. Nevertheless, regarding the strong association between platelet levels and ICIC, patients with thrombocytosis should receive initially both corticosteroids and antiplatelet agents.

Aged↗
PubMed2001

[Non-simultaneous malignant lymphoma and antiphospholipid syndrome: 4 cases].

OBJECTIVE: We report four cases of non-synchronous antiphospholipid syndrome (APS) and malignant lymphoma, which highlight the complex relationship that seems to exist between these illnesses. METHODS: In a retrospective study conducted in two departments (internal medicine and clinical hematology) of a university hospital, we collected all observations of patients with both APS and malignant lymphoma diagnosed throughout the past decade. RESULTS: An association of APS with malignant lymphoma was recorded in three female and one male patient, median age 42.5 years at the time of diagnosis of the first disease. In each case, the primary APS was diagnosed, with arterial thrombotic events in three cases and venous thrombotic events in one case. One patient had isolated IgG anticardiolipin antibody, whereas the others had a combination of IgG anticardiolipin antibody and lupus anticoagulant with or without IgG anti-beta 2 glycoprotein I antibody. One patient also had an acquired inhibitor to factor VIII:C and a chronic C virus hepatitis. The mean time apparently separating the two illnesses ranged from 18 months to 9 years, but in two cases the diagnosis of APS was delayed due to a progressive, atypical, neurological onset. In two instances, the APS took place at a distance from a cured malignant lymphoma (Hodgkin's disease and nodal large cell B-cell lymphoma), whilst in the others it preceded a B-cell lymphoma (nodal and cutaneous, small cells and primary hepatic, large cells). Treatment resulted in complete haematological response in both cases, with disappearance of anticardiolipin antibody and lupus anticoagulant in the latter following a double autologous peripheral blood stem cell transplantation. In addition, late carcinomas (breast, kidney, thyroid) were seen in two patients. CONCLUSIONS: Our data indicate that the diagnosis of a malignant lymphoma should be considered in patients with a primary APS and peripheral lymph node enlargement or unexplained constitutional symptoms. Conversely, a late onset of arterial or venous thrombotic diathesis after a malignant lymphoma may indicate not only late relapse of malignant lymphoma but also a subsequent APS.

Adult↗
PubMed2001

Delayed motherhood increases the probability of sons to be infertile.

PURPOSE: To ascertain whether advanced maternal age at birth is associated with offspring infertility. METHODS: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. RESULTS: Maternal age at birth (odds ratio 1.236, 95% CI 1.100-1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351-0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mother's age at birth increased (regression coefficient +/- standard error 0.212 +/- 0.059; P < 0.001), but decreased as birth order increased (regression coefficient +/- standard error -0.596 +/- 0.230; P = 0.010). CONCLUSIONS: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Female↗
PubMed2001

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

BACKGROUND: It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. METHODS: A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. RESULTS: The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. CONCLUSIONS: Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

Adult↗