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Y Garcia

Publications and source records attributed to Y Garcia.

15 recordsLinked to original sources
PubMed2006

[Treatment with intravenous rt-PA in a general hospital context: A review of the Saint-Jean Hospital experience from Perpignan, France].

INTRODUCTION: Intravenous recombinant tissue plasminogen activator (rt-PA) has approval for use despite of its authorization for treatment of ischemic stroke within the 3-hour time window in 2003, is rarely used in community hospital (CH). It therefore remains questionable if the positive results of the key studies conducted in specialized centers may be extended to community hospitals less specialized in the management of stroke. METHODS: We report the results of an observational cohort study including 39 patients treated with intravenous rt-Pa (according to the NINDS rt-PA stroke trail treatment protocol) at St Jean Hospital (Perpignan, France) between March 1, 2002 and August 31, 2005. Results are compared to those of the treated arm of the NINDS study. RESULTS: 1.2p.cent of ischemic stroke were treated with intravenous rt-Pa. Results are similar to those of the NINDS study: The outcome was favorable (modified Rankin score (mRS) with 0 or 1) for 44p.cent of the patients (as compared to 39p.cent in the NINDS study (X2 = 0.34; p = 0.5)) and there was no significant difference in term of death or outcome as assessed by mRS at 3 months (X2 = 0.09; p = 0.75 and X2 = 0.77; p = 0.75, respectively). No symptomatic hemmorrhagic transformation related to the use of rt-Pa was observed. CONCLUSION: Our results indicate that rt-PA therapy for ischemic stroke may be as safe and effective in the setting of a community hospital as it is in specialized centers.

Adult↗
PubMed2001

EXAFS and thermodynamics of Fe(II) spin transition polymeric compounds.

We have studied the temperature variations of the EXAFS spectra of three Fe(II)/triazole-based spin transition polymeric compounds compared to a monomer belonging to the same family. These compounds have various temperatures of transition and hysteresis loop widths. In the three polymers, the Fe-Fe-Fe alignment, detected by a multiple scattering signal at the double Fe-Fe distance, is preserved through the spin transition. For the four compounds, we have studied the variations versus temperature of the Debye-Waller factors for both FeN6 (first shell) and Fe-Fe-Fe (multiple scattering path, only for the polymers). We report a strong increase of (sigma2(FeN6) through the spin transition for the monomer and two of the polymeric species. For the polymers an increase of sigma2(Fe-Fe-Fe) is also observed. These observations confirm the results available in the literature, and we confirm the interpretation as an increase of the vibrational part of the DW. For one particular polymer, we observe an unexpected behaviour: no significant increase of the Debye-Waller factor from low spin to high spin states. The EXAFS study of these non mono-crystalline species is the only way to discuss the local structure-thermodynamics properties relationships, and particularly the so-called cooperative effect in the spin transition process.

Journal Article↗
PubMed2000

Synthesis, crystal structure, EXAFS, and magnetic properties of catena [mu-tris(1,2-bis(tetrazol-1-yl)propane-N1,N1')iron(II)] bis(perchlorate). First crystal structure of an iron(II) spin-crossover chain compound.

[Fe(btzp)3](ClO4)2 (btzp = 1,2-bis(tetrazol-1-yl)propane) represents the first structurally characterized Fe(II) linear chain compound exhibiting thermal spin crossover. It shows a very gradual spin transition (T1/2 = 130 K) which has been followed by magnetic susceptibility measurements and 57Fe Mössbauer spectroscopy. The structure has been solved at 200 and 100 K by single-crystal X-ray analysis. It crystallizes in the trigonal space group P3c1 with Z = 2 Fe(II) units at both temperatures. The molecular structure consists of chains running along the c axis in which the Fe(II) ions are linked by three N4,N4' coordinating bis(tetrazole) ligands. The main difference between the two forms appears to be in the Fe-N bond lengths, which are 2.164(4) A at 200 K and 2.038(4) A at 100 K. The Fe-Fe separations are 7.422(1) A at 200 K and 7.273(1) A at 100 K. The EXAFS results are consistent with the crystal structure. In both spin states, the FeN6 octahedron is almost regular within the EXAFS resolution. The Fe-N distance is found as 2.16(2) A at 300 K and 2.00(2) A at 40 K. The absence of the "7 A peak" in the EXAFS spectra of [Fe(btzp)3](ClO4)2, in contrast with what has been observed for the [Fe(4-R-1,2,4-triazole)3]-(anion)2 chain compounds, confirms that this peak can be used as the signature of a metal alignment only when it involves a strongly enhanced multiple scattering M-M-M path, with M-M spacing less than 4 A. Irradiation with green light at 5 K has led to the population of the metastable high-spin state for the iron(II) ion. The nature of the spin-crossover behavior has been discussed on the basis of the structural features.

Journal Article↗
PubMed2000

Immunogenicity comparison of a multi-antigenic peptide bearing V3 sequences of the human immunodeficiency virus type 1 with TAB9 protein in mice.

The multiple antigenic peptide system (MAP) has been proposed as a novel and valuable approach for eliciting antibodies for peptides and developing synthetic vaccines. Multi-epitope polypeptides (MEP) have also been developed as an alternative to the recombinant approach for vaccines. The V3 loop from the HIV type 1 (HIV-1) external glycoprotein (gp120) contains the principal neutralization domain (PND). Antibodies against this region neutralize HIV-1 in vitro and in vivo. In this work, a novel presentation of di-epitope MAP was synthesized. A monomeric MAP carrying two identical JY1 V3 sequences as B-cell epitopes and the 830-843 region of tetanus toxoid as a T-helper cell epitope was synthesized. This basic structure was covalently linked to produce a four-JY1-branched homodimer (JY1-MAP4). Additionally, six different monomeric MAPs, bearing four copies of V3 from isolates LR150, JY1, RF, MN, BRVA and IIIB, were synthesized. These monomers were conveniently linked among themselves to produce homodimeric and heterodimeric MAPs of eight V3 branches (V3-MAP8). JY1-MAP8 elicited higher antibody titers in Balb/c mice than JY1-MAP4. The immunogenicity of two different, hexavalent V3-MAP8 mixtures and the MEP TAB9, which tandems the same six V3 sequences in a single molecule, were compared. The antibody response against the mixtures of the heterodimeric MAP showed a wider recognition pattern of the V3 region, while the homodimeric cocktail showed an intermediate pattern. Antibodies elicited by TAB9 recognized only the JY1, LR150 peptides. These results emphasize the influence of V3 epitope presentation upon the characteristics of the antibody response generated.

Amino Acids↗
PubMed1999

Relationship between O6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients.

BACKGROUND: Adjuvant nitrosourea chemotherapy fails to prolong survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O6-methylguanine DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. METHODS: We evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical responses of the patients to CENU-based chemotherapy. RESULTS: Eight tumor samples had no detectable MGMT, whereas other samples had from 9,989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The Mer- patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer+ patients (MGMT > 60,000 molecules/nucleus) (X2 = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the median time to progression (TTP) of Mer+ patient was shorter than that of Mer- patient (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = 2.26, p = 0.029). However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). CONCLUSION: This study suggests that being MGMT positive is indicative of a more aggressive disease that progresses more rapidly with CENU therapy. However, MGMT negative tumors are not always sensitive to CENU agents, suggesting that other factors are also important.

Adult↗
PubMed1998

Clinical response of O(6)-methylguanine-DNA methyltransferase levels to 1,3-(2-chloroethyl)-1-nitrosourea chemotherapy in glioma patients.

Adjuvant nitrosourea chemotherapy fails to prolong patient survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O(6)-methylguanine-DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. The authors evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical response of the patients to CENU-based chemotherapy. The patients were treated with CENU after evidence of progressive disease following surgery and radiotherapy. Eight tumor samples had no detectable MGMT, whereas other samples had from 9989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The median time to progression (TTP) was 6.7 months with a median survival of 13 months. The Mer(-) patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer(+) patients (MGMT > 60,000 molecules/nucleus) (chi-square = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the TTP of Mer(+) patients was shorter than that of Mer(-) patients (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = -2.26, p = 0.029). The TTP and survival time in the effective GBM group were also longer than those in the progressive GBM group. However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). Results from this study suggested that MGMT positivity is indicative of more aggressive disease that progresses more rapidly when exposed to CENU therapy. However, MGMT-negative tumors are not always sensitive to CENU agents, suggesting that other factors may also be important.

Journal Article↗
PubMed1997

Excitatory sulfur-containing amino acid-induced release of [3H]GABA from rat olfactory bulb.

The effect of L-cysteine sulfinic acid (CSA) and L-homocysteic acid (HCA) on the release of tritiated gamma-amino butyric acid ([3H]GABA), from the external plexiform layer (EPL) of the rat olfactory bulb, was compared with that of glutamate. These amino acids induced release of GABA was strongly inhibited by the glutamate uptake blocker, pyrrolidine-2,4-dicarboxylate (2,4,PDC) (50 microM), while it was not inhibited by the specific GABA uptake blockers nipecotic acid (0.5 mM) or NO-711 (5 microM). Only the HCA induced GABA release was 60% inhibited by beta-alanine (0.5 mM), a glial GABA uptake blocker and 78% by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) (100 microM). The non-NMDA receptor antagonists 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX) up to 500 microM had no effect on HCA or CSA stimulated GABA release. These results bring evidence for an excitatory role of HCA and CSA together with glutamate on GABAergic neuronal or glial elements, in the olfactory bulb. This role could be mediated through the reversal of the glutamate or/and the glial GABA transporter and through the activation of a NMDA type receptor.

Animals↗
PubMed1997

O6-Alkylguanine-DNA alkyltransferase in normal colon tissue and colon cancer.

O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that reverses alkylation damage produced by chloroethylnitrosoureas and is a major determinant of cellular resistance to adjuvant chemotherapy with these drugs. AGT activity was measured in 119 samples from 69 patients, including normal, tumor, and diseased tissue, and 42 patients in which both normal and tumor tissue were assayed. The activity varied among individuals, but there was no statistically significant difference in average AGT activity among tumor, normal, and diseased tissue, or between men and women, or between young and old patients (< 70 or > 70 years). Few (3/49) tumor samples showed an absence of AGT activity (Mer- phenotype). The results indicate that nearly all colon cancers have significant AGT activity, and adjuvant chloroethylnitrosoureas chemotherapy must be modified, perhaps by the use of AGT biochemical modulators, to overcome this natural drug resistance.

Adolescent↗
PubMed1996

Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.

PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

Adenocarcinoma↗
PubMed1996

A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer.

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.

Adult↗
PubMedDate not supplied

Peritoneal macrophage cytotoxicity induced by serum in vitro.

The authors studied the effects of peritoneal macrophages on the growth of HP2 cells, a continuous line isolated from the transplanted Harding-Passey mouse melanoma. They found that normal peritoneal macrophages can exert a strong cytostatic effect on HP2 cells, as expressed by cell number and tritiated thymidine uptake by the target cells. The data indicates that normal heat inactivated sera from various species can render macrophages cytostatic. In addition, normal serum can amplify the cytostatic properties of macrophages from immunized animals. The results are discussed in the light of present knowledge of macrophage metabolism.

Animals↗