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Biomedical subjects

E Grau

Publications and source records attributed to E Grau.

At least 19 recordsLinked to original sources
PubMed2004

Minimal residual disease in neuroblastoma: to GAGE or not to GAGE.

We assessed the utility of GAGE gene expression as a marker of minimal residual disease (MRD) in neuroblastoma. The GAGE gene family shows a high degree of homology (>90%), clustering into two subgroups. GAGE-1, -2, and -8 form one subset, almost identical among themselves, while GAGE-3 to -7 constitute the other subset. The entire GAGE family (GAGE-1-8) was studied by RT-PCR followed by Southern blotting to increase both the sensitivity and specificity of the technique. Surprisingly, expression of GAGE was detected in 59% of peripheral blood samples from normal controls (20/35) as well as in a similar proportion from neuroblastoma patients with localized disease (stages 1 and 2). The study of GAGE-1, -2, and -8 with specific primers lowered this percentage to 28% (10/35), of which only two (6%) showed a high level of expression (directly visualized after RT-PCR). We conclude that GAGE genes can show a variable, usually low level of illegitimate expression in normal blood cells, and therefore their use as MRD markers should be taken with caution.

Antigens, Neoplasm↗
PubMed2003

LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.

Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.

Animals↗
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↗
PubMed2001

Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice.

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired.

Action Potentials↗
PubMed2001

Monitoring of endocrine disruptors in surface waters by the yeast recombinant assay.

Endocrine disruptors exert physiological effects at very low concentrations. Surface waters present often a mixture of high concentrations of low-potency disruptors and low amounts of very powerful ones, making their chemical analysis complicated and expensive. We developed a recombinant yeast assay (RYA) for estrogenic compounds using 96-well microtiter plates. This assay is based on three yeast strains, transformed with self-propagating plasmids. One strain contains an expression plasmid for the human estrogen hormone receptor and an appropriate reporter; it detects estrogenic and antiestrogenic activities. The two other yeast strains, one expressing the human progesterone receptor and a second based on the yeast activator Gal4p, served to analyze the nature of antiestrogenic activities. We applied this technique to water samples from two tributaries on the Llobregat river (NE Spain) as well as from four sewage treatment plants discharging on them. Our results indicate that the efficiency of sewage treatment plants for eliminating estrogenic compounds varied notably, being in at least one case completely inefficient. We also observed a prevalence of an inhibitory activity all through the two rivers; this inhibition was hormone specific. These results were consistent to previously obtained chemical analyses of the same samples, although chemical and in vivo analyses showed rather different levels of sensitivity for some compounds. Our findings demonstrate the utility of the yeast recombinant assay for analyzing complex natural samples; at the same time, they stress the necessity of a panel of different yeast systems to adequately describe endocrine-disruptor activities.

Algorithms↗
PubMed2000

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.

Adenosine Triphosphate↗
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↗
PubMed1999

Laparoscopic colorectal cancer resection: initial follow-up results.

An observational prospective cohort study was made to evaluate the results of laparoscopic colorectal cancer resection, in terms of recurrence and patient survival. Fifty consecutive patients were analyzed, subjected to abdominoperineal amputations of the rectum (n = 10), anterior rectal resection (n = 13), rectosigmoidectomy (n = 18), and other colectomies (right, left, segmentary) (n = 9). Mean follow-up was 21 months (maximum, 42 months). The tumors corresponded to stage I (TNM classification of the International Union Against Cancer) in 6 cases, stage II in 17, stage III in 18, and stage IV in 9 cases. Survival in stages I-IV was 100, 92, 79, and 18%, respectively, with a disease-free survival rate of 100, 70, and 49% in stages I-III, respectively. Recurrence was pelvic in four cases, with multiple growths, peritoneal carcinomatosis, lung metastases, and implantation in the port scar in one case each. To conclude, survival after a maximum follow-up period of 42 months was found to be acceptable and similar to the percentages reported in the literature for open surgery.

Aged↗
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↗