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Biomedical subjects

E Pastor

Publications and source records attributed to E Pastor.

At least 19 recordsLinked to original sources
PubMed2003

Tau phosphorylation and kinase activation in familial tauopathy linked to deln296 mutation.

Tau phosphorylation has been examined by immunohistochemistry in the brain of a patient affected with familial tauopathy with progressive supranuclear palsy-like phenotype linked to the delN296 mutation in the tau gene. Phospho-specific tau antibodies Thr181, Ser202, Ser214, Ser396 and Ser422, and antibodies to glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) and to phosphorylated (P) mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), p38 kinase (p38) and GSK-3betaSer9 have been used to gain understanding of the identification of phosphorylation sites, as well as of the specific kinases that regulate tau phosphorylation at those specific sites, in a familial tauopathy. The neuropathological examination disclosed atrophy of the right precentral gyrus and the brainstem. Neurone loss and gliosis were observed in the substantia nigra, several nuclei of the brainstem and diencephalon. Hyper-phosphorylated tau accumulated in neurones with neurofibrillary tangles and in neurones with pretangles in the substantia nigra, locus ceruleus, peri-aqueductal grey matter, reticular formation, motor nuclei of the brainstem, and thalamus, amygdala and hippocampus. tau-immunoreactive astrocytes and, particularly, oligodendrocytes with coiled bodies were widespread in the brainstem, diencephalons, cerebral white matter and cerebral cortex. Increased expression of MAPK/ERK-P, SAPK/JNK-P, p-38-P and GSK-3beta-P was observed in select subpopulations of neurones with neurofibrillary tangles and in neurones with pretangles. MAPK/ERK-P, SAPK/JNK-P, p38-P and GSK-3beta-P were also expressed in tau-containing astrocytes and in oligodendrocytes with coiled bodies. These findings show, for the first time, activation of precise kinases that regulate tau phosphorylation at specific sites in familial tauopathy.

Adult↗
PubMed2001

Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene.

Heterozygous missense and splice-site mutations in the tau gene have been previously identified in familial frontotemporal dementia with autosomal dominant inheritance. Here we report a Spanish kindred in which two brothers born from a third-degree consanguineous marriage were both affected with atypical progressive supranuclear palsy. A homozygous deletion at codon 296 (delN296) was identified in one of the affected siblings. Among the heterozygous carriers, two members with probable Parkinson's disease were identified, but none of heterozygotes developed atypical parkinsonism. The delN296 mutation lies in the sequence corresponding to the second tubulin-binding repeat of tau protein and affects one asparagine residue absolutely conserved in other species. This finding indicates that homozygous mutations in the tau gene may also cause hereditary tauopathies.

Adult↗
PubMed2001

Home treatment of deep venous thrombosis with low molecular weight heparin: Long-term incidence of recurrent venous thromboembolism.

Outpatient treatment of deep venous thrombosis (DVT) with low molecular weight heparin (LMWH) seems as safe and effective as inpatient treatment with unfractionated heparin (UFH). However, most of the randomized trials comparing a LMWH with UFH described clinical outcomes within 3-6 months. The long-term incidence of recurrent VTE after treatment of DVT with LMWH remains to be established. The primary objective of this retrospective study was to document the long-term incidence of recurrent venous thromboembolism (VTE) in patients with DVT treated with a LMWH, nadroparin in an outpatient basis. The patients were evaluated 46 months after inclusion in two cohorts comparing home treatment with nadroparin (n = 130) with in-hospital treatment with intravenous UFH (n = 149). More than 60% of the patients in the nadroparin group could be treated at home, either entirely or after a short stay in hospital. The age-adjusted thrombosis-free survival was not statistically significant between nadroparin and UFH-treated patients (P = 0.084). There was a nonsignificant trend favoring nadroparin as compared with UFH. The hazard ratio (HR) for recurrent VTE in the nadroparin group with respect to the UFH group was 0.44 (95% confidence interval, 0.17-1.12). No significant differences were observed in overall mortality or major hemorrhage between the two treatment groups. Our study suggests that home treatment of DVT with LMWH is at least as effective and safe as in-hospital UFH after a long-term follow-up period.

Adult↗
PubMed2000

Dinuclear azolato-bridged complexes of the nickel group metals with haloaryl ligands: a reinvestigation of their behavior in solution.

A reinvestigation of the NMR spectra of the complexes (NBu4)2[M2(mu-LL)2R4] (M = Pd, Ni, Pt, LL = pyrazolate (pz), 3,5-dimethylpyrazolate (dmpz), 3-methylpyrazolate (mpz), indazolate (indz), R = C6F5; M = Pd, LL = pz, dmpz, mpz, indz, R = 2,4,6-C6F3H2) shows that the boat-shaped dimeric structures of their anions are quite stable in solution, and the previously proposed fast equilibria or dissociations to give species such as [R2M(N-N)(acetone)]-, [R2M(acetone)2] + 2dmpz-, or [R2M(N1-N2)(acetone)]- + [R2M(N2-N1)(acetone)]- in no case occur. A mixture of the two diastereoisomers (head-to-head, HH, and head-to-tail, HT) is present for the asymmetrically substituted azolates (mpz and indz), in a ratio ranging from 1:7 to 1:30 for the different complexes. Strong through-space coupling between the endo ortho fluorine nuclei of different MR2 fragments is observed in the 19F NMR spectra of these diastereoisomers whose boatlike structures place these atoms at short distances.

Journal Article↗
PubMed2000

[Primary stent implantation in aortic coarctation: mid-term follow-up].

BACKGROUND: The use of balloon-expandable stents provides an effective alternative therapy in patients with stenotic lesions in congenital heart disease. Stents implantation has served to improve the results and to reduce complications of balloon angioplasty for coarctation and recoarctation of the aorta. OBJECTIVE: We report our results after primary stents implantation for coarctation and recoarctation of the aorta. PATIENTS AND METHODS: Balloon-expandable stents were implanted in 14 patients (mean age 20 +/- 12 years) with coarctation of the aorta (11 native and 3 postoperative); 2 patients had associated malformations. The morphology varied: 10 resembled a located-diaphragm (one of them with moderate arch hypoplasia); 2 had distorted coarctation and 2 had a complete aortal obstruction. Five patients were hypertensive and 1 had cardiogenic shock and severe arrhythmias which did not respond to intensive medical therapy. In all cases 14 Palmaz stents (7 P308 and 7 P4014) were implanted with the primary technique through a Mullin's sheath. The balloon-to-descending aorta diameter ratio, measured at the level of the diaphragm, was 1. A special technique was carried out in the 2 cases with complete aortal obstruction. RESULTS: The procedure was effective in all 14 cases. The coarctation diameter increased from 4 +/- 2 to 15 +/- 2 mm (p < 0.0001) and transcoarctation systolic pressure gradient decreased from 43 +/- 19 to 2 +/- 2 mmHg (p < 0.0001). The ratio of the coarctation to descending aorta diameter measured at the level of the diaphragma increased from 0.3 +/- 0.1 to 0.95 +/- 0.05 (p < 0.001). At 19 +/- 8 months follow up, all patients showed sustained clinical improvement. The patient with complete aortal obstruction experienced a dramatic improvement, but she died from a sudden cardiac event 22 months after the procedure. At angiographic follow up in 7 patients, 1 year after implantation, no recoarctation was observed with secondary vessels patent, and absence of restenosis. CONCLUSIONS: a) Percutaneous endovascular stents implantation in coarctation and recoarctation of the aorta may become an effective treatment modality in the older child, adolescent and adults; b) stents are particularly attractive in those patients with a more complex anatomy and higher surgical risk; c) primary stenting is expected to have a lower rate of complications, and d) we describe a special technique with a right femoral-left humeral arterial circuit that is successfully applied to patients with complete aortal obstruction.

Adolescent↗
PubMed2000

[PRIMARY STENT IMPLANTATION IN AORTIC COARCTATION. MID-TERM FOLLOW-UP]

The use of balloon-expandable stents provides an effective alternative therapy in patients with stenotic lesions in congenital heart disease. Stents implantation has served to improve the results and to reduce complications of balloon angioplasty for coarctation and recoarctation of the aorta. AIM: We report our results after primary stents implantation for coarctation and recoarctation of the aorta. PATIENTS AND METHODS: Balloon-expandable stents were implanted in 14 patients (mean age 20 +/- 12 years) with coarctation of the aorta (11 native and 3 postoperative); 2 patients had associated malformations. The morphology varied: 10 resembled a located-diaphragm (one of them with moderate arch hypoplasia); 2 had distorted coarctation and 2 had a complete aortal obstruction. Five patients were hypertensive and 1 had cardiogenic shock and severe arrhythmias which did not respond to intensive medical therapy. In all cases 14 Palmaz stents (7 P308 and 7 P4014) were implanted with the primary technique through a Mullin's sheath. The balloon-to-descending aorta diameter ratio, measured at the level of the diaphragm, was 1. A special technique was carried out in the 2 cases with complete aortal obstruction. RESULTS: The procedure was effective in all 14 cases. The coarctation diameter increased from 4 +/- 2 to 15 +/- 2 mm (p < 0.0001) and transcoarctation systolic pressure gradient decreased from 43 +/- 19 to 2 +/- 2 mmHg (p < 0.0001). The ratio of the coarctation to descending aorta diameter measured at the level of the diaphragma increased from 0.3 +/- 0.1 to 0.95 +/- 0.05 (p < 0.001). At 19 +/- 8 months follow up, all patients showed sustained clinical improvement. The patient with complete aortal obstruction experienced a dramatic improvement, but she died from a sudden cardiac event 22 months after the procedure. At angiographic follow up in 7 patients, 1 year after implantation, no recoarctation was observed with secondary vessels patent, and absence of restenosis. CONCLUSIONS: a) Percutaneous endovascular stents implantation in coarctation and recoarctation of the aorta may become an effective treatment modality in the older child, adolescent and adults; b) stents are particulary attractive in those patients with a more complex anatomy and higher surgical risk; c) primary stenting is expected to have a lower rate of complications, and d) we describe a special technique with a right femoral-left humeral arterial circuit that is successfully applied to patients with complete aortal obstruction.

Journal Article↗
PubMed1999

Recurrent venous thromboembolism in a Spanish population: incidence, risk factors, and management in a hospital setting.

The major concern in the management of venous thromboembolism is the propagation of thrombus and rethrombosis. The incidence of recurrences and the duration of oral anticoagulant therapy in these patients are still controversial. The aim of this study was to determine the incidence, timing, and outcome of further thrombotic events after an initial episode of venous thromboembolism in a hospital setting. In addition, we evaluated potential risk factors for all these outcomes. This was designed as a retrospective analysis of all patients admitted to our Center with an episode of deep vein thrombosis and/or pulmonary embolism between 1986 and 1996. The patients included in the study had to be treated with unfractionated heparin or low molecular weight heparin, followed by at least 3 months of oral anticoagulants. Natural and acquired hemostasis inhibitors were assayed in patients aged less than 50 years. A total of 290 patients with a first episode of venous thromboembolism were included in the study. A total of 33 patients (11.9%, 95% confidence interval. 7.4-14.6) had recurrent episodes. The cumulative incidence of recurrent venous thromboembolism after 2, 5, and 10 years was 7.68, 10, and 12.4%, respectively. The incidence of rethrombosis was significantly higher in patients with idiopathic venous thromboembolism than in patients with secondary thrombosis. Abnormalities of hemostasis were found in 54.5% (95% confidence interval, 37.6-71.4) of the patients with recurrences and under the age of 50 years. Three of seven patients who stopped anticoagulant therapy after the second episode presented a third thrombotic event. In our study population, those patients with idiopathic venous thromboembolism seem to have an increased risk of recurrence. The second thrombotic episode occurs more frequently during the following 2 years after cessation of anticoagulation therapy. Our findings strongly support the use of long-term anticoagulant therapy in patients with recurrent venous thromboembolism.

Aged↗
PubMed1999

Monitoring oral anticoagulant treatment from plasma stored for up to 48 hours and frozen plasma.

BACKGROUND AND OBJECTIVE: The number of patients being referred for lifelong anticoagulant treatment has increased markedly in the last years. The prothrombin time test is sometimes difficult to perform the same day as sample collection. The aim of this study is to determine International Normalized Ratio (INR) and vitamin-K dependent factor levels of frozen plasma and plasma stored for up 48 hours. DESIGN AND METHODS: The INR of 84 patients receiving acenocoumarol were determined fresh (0 hours), on samples stored between 2 degrees C and 8 degrees C for 24 hours and 48 hours, and on frozen samples (-40 degrees C) using 4 different thromboplastin reagents (Thromboplastin IS; Thromborel; Simplastin; and Thromboplastin D+G). In addition, factors II, VII, IX, X were determined in 34 of these patients in all these situations. We used the interclass correlation coefficient to compare the results obtained at 0 hours and the results obtained in the subsequent measurements. Both measurement and proportional errors were also estimated by linear regression analysis. RESULTS: The correlation coefficient of the INR between fresh and frozen plasma was 0.98, 0.98, 0.92 and 0.97 for IS, Thromborel, Simplastin and D+G respectively. The correlation between 0 and 24 hours was 0. 98, 0.91, 0.95 and 0.85 for IS, Thromborel, Simplastin and D+G respectively. By 48 hours although IS still had r=0.94, Thromborel, Simplastin, and D+G had r=0.55, r=0.50 and r=0.81, respectively. By 24 hours in stored plasma and in frozen plasma the activity of vitamin-K dependent factors was slightly reduced (r=0.97 at 24h/r=0. 94 with frozen plasma for factor II, r=0.92/0.96 for factor VII, r=0. 83/0.98 for factor IX, and r=0.98/0.95 for factor X). By 48 hours however, significant reductions were noted in the activity of these factors (r=0.94 for factor II, r=0.88 for factor VII, r=0.70 for factor IX, and r=0.98 for factor X). INTERPRETATION AND CONCLUSIONS: The INR can be reliable determined in frozen plasma and in plasma stored at 2-8 degrees C for up to 24 hours.

Administration, Oral↗
PubMed1998

Home treatment of deep vein thrombosis: a two-years experience of a single institution.

BACKGROUND AND OBJECTIVE: Low molecular weight heparin (LMWH) is known to be safe and effective for the initial treatment of patients with acute deep-vein thrombosis (DVT). Moreover, LMWH allows patients to be treated at home. However, only limited data are available on the feasibility of LMWH treatment at home in daily clinical practice. DESIGN AND METHODS: We evaluated the feasibility, efficacy and safety of home treatment of DVT in a consecutive series of outpatients using LMWH over a two year period. The two main reasons for exclusion were concomitant pulmonary embolism and a high hemorrhagic risk. Patients were treated with 95 IU/kg bid of nadroparin for a minimum of 7 days. The study design allowed patients to go home immediately after diagnosis or to be discharged after a short hospital stay. Anticoagulation with acenocoumarol was started 2 days before discontinuing nadroparin. RESULTS: From 1995 to 1997, 71 consecutive outpatients with DVT were treated with nadroparin. Ambulatory treatment was feasible in 39 patients (24 patients did not require admission and 15 patients were discharged in less than 48 hours). The remaining 32 patients were treated in hospital. The main causes for admission were the presence of serious comorbid conditions, the severity of symptoms in the involved leg and the inability to obtain a diagnosis. None of the patients had clinical recurrent venous thromboembolism during the initial treatment with nadroparin. One patient receiving nadroparin at home had a non-fatal major bleeding. None of the patients to whom the possibility of home therapy was offered wished to remain at hospital. However, only 26% of the home-treated patients injected the drug by themselves. INTERPRETATION AND CONCLUSIONS: Home therapy of DVT with LMWH bid at doses adjusted to patient's body weight is feasible, efficient and safe. Over 50% of outpatients with DVT can be treated at home, either entirely or after a short stay in hospital. Nevertheless, before using this therapeutic alternative as a standard of practice, an adequate assessment of embolic and hemorrhagic risks, and comorbid conditions, should be made.

Adult↗
PubMed1998

Elective splenectomy in relapsing thrombotic thrombocytopenic purpura.

Between 20 and 40% of surviving patients with thrombotic thrombocytopenic purpura (TTP) have relapses. Plasma exchange therapy is usually effective in treating relapses, but this treatment does not prevent TTP recurrence. The role of splenectomy in relapsing TTP is still controversial. We describe a patient with multiple relapses of TTP who was successfully treated with elective splenectomy.

Adult↗