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Biomedical subjects

P Sanchez

Publications and source records attributed to P Sanchez.

At least 19 recordsLinked to original sources
PubMed2003

Characterization of soluble polymer supported organic compounds by LC/electrospray ionization MS toward a complete automation of the liquid-phase process in combinatorial chemistry.

In the case of a soluble polymer supported synthesis, the tuning of the support solubility depending on the solvent offers new opportunities for combinatorial chemistry for two reasons. First, organic syntheses in solution are generally easily translated on a soluble polymer supported substrate. Second, complete automation of the three successive steps of combinatorial chemistry (synthesis, analytical control, biological test) is approached without releasing the synthesized compound from the support. We report in this paper the preliminary results toward automation of both soluble polymer supported syntheses and their subsequent monitoring by ESI mass spectrometry.

Automation↗
PubMed2001

Quantitative determination of rocuronium in human plasma by liquid chromatography-electrospray ionization mass spectrometry.

Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) was used for the quantification of the neuromuscular blocking agent rocuronium in human plasma. Verapamil was used as internal standard. The samples were subjected to a dichloromethane liquid-liquid extraction after ion pairing of the positively charged ammonium compound with iodide prior to LC-MS. Optimized conditions involved separation on a Symmetry Shield RP-18 column (50 x 2.1 mm, 3.5 microm) using a 15-min gradient from 10 to 90% acetonitrile in water containing 0.1% trifluoroacetic acid at 250 microl/min. Linear detector responses for standards were observed from 25 to 2,000 ng/ml. The extraction recovery averaged 59% for rocuronium and 83% for the internal standard. The limit of quantification (LOQ), using 500 microl of plasma, was 25 ng/ml. Precision ranged from 1.3 to 19% (LOQ), and accuracy was between 92 and 112%. In plasma samples, at 20 and 4 degrees C, rocuronium was stable at physiological pH for 4 h; frozen at -30 degrees C it was stable for at least 75 days. The method was found suitable for the analysis of samples collected during pharmacokinetic investigations in humans.

Androstanols↗
PubMed2001

Beta-blocker treatment in heart failure.

Heart failure treatment has markedly changed during the last few decades, with demonstration of benefit of afterload reduction by vasodilator therapy and introduction of the concept of the deleterious consequences of the neuro-hormonal compensatory stimulation. Blockade of beta-adrenergic receptors, initially contra-indicated in heart failure, provide a marked reduction of mortality and morbidity in combination with diuretics and angiotensin-converting enzyme inhibitors, as demonstrated in many clinical trials. We performed a review of all clinical trials that compare beta-blockers vs. placebo in chronic heart failure. Beta-blockers with different pharmacological profiles have been tested, mainly metoprolol, bisoprolol, bucindolol and carvedilol. With progressive dose increment, tolerance of such treatment was generally good, left ventricular function improved, hospitalisations for heart failure were less frequent and mortality was reduced. The meta-analysis of the 16 randomised trials, with at least one death in each treatment group, provides a 24% relative risk reduction for such hospitalisations (95% CI=19%-29%) and 22% reduction for mortality (95% CI=16%-28%). Heterogeneity of beta-blocker effect for mortality was found and related to the non-significant benefit obtained in the BEST trial with bucindolol. When such a trial is excluded, the effect model analysis shows that relative risk reduction (beta-blocker induced benefit) is constant whatever the severity of the disease. The mechanism of beta-blocker induced benefit remains unclear, but is at least partly related to left ventricular function improvement and prevention of severe ventricular arrhythmias. In conclusion, beta-blocker treatment has become an established therapy for heart failure, in combination with diuretics and ACE inhibitors. Complementary informations will be needed to clarify the mechanism of benefit and to define the best therapeutic strategy according to the individual characteristics of patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2001

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS).

BACKGROUND: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation. OBJECTIVE: Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation. METHODS: A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications. RESULTS: The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003). CONCLUSION: The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.

Administration, Oral↗
PubMed2001

[Does statin therapy reduce the risk of stroke? A meta-analysis].

Large scale clinical trials have clearly demonstrated that the HMG-CoA reductase inhibitors (statins) reduce cardiovascular mortality by about 30%. The specific benefit on stroke prevention remains however to be determined. We reviewed all controlled clinical trials comparing statins versus placebo in primary and secondary prevention of cardiovascular disease. We identified 13 studies including 4S, CARE, WOSCOPS and LIPID. More than 32000 patients were randomized. The meta-analysis was performed using relative risk as treatment effect parameter. Statin treatment induced a significant relative risk reduction (RRR) of 24% (95% CI [12%-34%]) for stroke (2.1% vs 2.8%). RRR achieved 25% (95% CI [17%-32%]) for cardiovascular mortality and 34% (95% CI [30%-38%]) for myocardial infarction, without heterogeneity between trials. Stroke was reduced by 25% in secondary prevention, and by 15% in primary prevention, without significant heterogeneity between them. RRR of stroke was similar with pravastatin (RRR=0.79, p=0.0038) and with simvastatin (RRR=0.71, p=0.049). The effect model analysis (relationship between annual incidence of events in treated group versus placebo group in each trial) showed that RRR was constant whatever the baseline risk. These results are in favor of a preventive efficacy of statin treatment against stroke in middle aged patients with coronary heart disease. Complementary information will be needed to clarify the mechanism of this beneficial effect and to demonstrate statin efficacy in a population with a higher risk of stroke such as the elderly.

Age Distribution↗
PubMed2000

The use of alternative systems for the ecotoxicological screening of complex mixtures on fish populations.

This paper presents the results of the use of alternative systems in a screening study of four complex mixtures. The following tests were performed: in vitro induction of micronuclei in a rainbow trout-derived cell line by flow cytometry, and hatching percentage, time of hatching and teratogenic alterations on the embryolarval development on medaka fish eggs. The results obtained with the proposed tests in this study allows an increase in the information level in a short period of time (2 weeks), using very low sample volumes (< 100 ml). Inclusion of chronic and specific effects (genotoxicity and teratogenicity) allows the selection of the most sensitive endpoint to increase security factors in the ecotoxicological assessment of complex mixtures, so that detailed studies can be focused only on those samples which require further research.

Animals↗
PubMed2000

Management of parapneumonic collections in infants and children.

BACKGROUND/PURPOSE: Video-assisted thoracoscopic surgery (VATS) has a recognized role in treatment of empyema thoracis. The purpose of this report is to show the value of initial VATS as the primary treatment of parapneumonic collections. METHODS: A retrospective review was done of 139 children who required surgical consultation for parapneumonic collections between January 1992 and July 1998. Management options were (M1) thoracentesis, chest tube drainage, or fibrinolytic therapy and delayed thoracotomy for unresolved collections; (M2) thoracentesis, chest tube drainage, fibrinolytic therapy with delayed VATS if the child remained ill; or (M3) primary VATS. Comparative data included age, duration of prehospital illness, oxygen requirements, white blood cell count, bacterial culture results, number of procedures performed per patient, duration of chest tube drainage, complications, and length of stay. Kruskal-Wallis 1-way analysis was used, with significance at P less than .05. RESULTS: A total of 60 children were treated by M1, 38 by M2, and 41 by M3. Age, duration of prehospital illness, oxygen requirements, white blood cell count, bacterial culture results, and complication rates were comparable. The median length of stay was 12 days for M1, 11 days for M2, and 7 days for M3, with M3 significantly shorter at P<.001. The number of procedures was a median of 2 in M1, 2 in M2, and 1 in M3, with M3 significantly fewer at P<.001. Duration of chest tube drainage was a median 5 days for M1 and 3 days for M2 and M3, with M1 significantly longer at P<.001. There were 9 thoracotomies in the M1 group, 3 in the M2 group, and none in the M3 group. One child in M3 required a second VATS. CONCLUSIONS: Primary VATS has significantly decreased the number of procedures, duration of chest tube drainage and length of stay for children with parapneumonic effusions. Primary VATS appears to be of value in management of bacterial pneumonia with effusion.

Chest Tubes↗
PubMed2000

AtBI-1, a plant homologue of Bax inhibitor-1, suppresses Bax-induced cell death in yeast and is rapidly upregulated during wounding and pathogen challenge.

Extensive searches have so far failed to identify functional plant homologues of the mammalian apoptotic machinery. Here we report the isolation and characterisation of an Arabidopsis thaliana homologue of human Bax Inhibitor-1, AtBI-1, isolated during a differential screen of plants challenged with the phytopathogen Pseudomonas syringae. AtBI is a member of a small gene family in Arabidopsis, members of which display extensive amino acid identity to human BI-1. AtBI-1 is also functionally similar to BI-1 in its ability to suppress the lethal phenotype in yeast conferred by expression of the mammalian proapoptotic protein, Bax. Expression of AtBI-1 is rapidly upregulated in plants during wounding or pathogen challenge, suggesting a role in responses to biotic and abiotic stress. AtBI-1 upregulation appears R gene independent and is not markedly affected by mutations required for specific classes of R genes. However, the accumulation of AtBI-1 message is significantly reduced in coi1, in which defence responses to insects, pathogens and wounding are compromised.

Amino Acid Sequence↗
PubMed2000

The level of expression of mu heavy chain modifies the composition of peripheral B cell subpopulations.

The B cell receptor (BCR) has a decisive role in transducing signals required for the development of B cells and their survival in the periphery. However, the processes that initiate these signals remain unclear and concepts of constitutive and ligand-dependent signaling have been proposed. Using a mu-transgenic mouse model, we have analyzed the impact of high surface IgM expression on the composition of the splenic B cell population. kappa-deficient mice homozygous for the H3-mu transgene have B cells with a higher BCR surface density than H3 heterozygous mice. This higher BCR expression is associated with an increase in the percentage and the total number of splenic B cells. In addition, an important proportion of CD23(-)CD21(+) marginal zone (MZ) B cells can be observed in H3 homozygous mice. However, these modifications operate in the absence of impairment of the positive selection process of the H3-mu/lambda1 combination over the H3-mu/lambda2 + 3 ones. These results suggest that (i) a constitutive BCR signaling directly correlated with BCR surface density is responsible for the efficient B cell colonization of the periphery with an accumulation of B cells in the MZ and (ii) a ligand-dependent BCR signal is responsible for the clonotype composition of the mature B cell repertoire.

Animals↗
PubMed2000

Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes.

Using an 'oligoclonal' model, we have previously shown that mice transgenic for a mu chain (H3) and deficient for kappa chain expression display a mature B cell repertoire largely dominated by the H3/lambda1 pair, while the four H3/lambda available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL lambda locus coding for a defective lambda1 chain (lambda1(s)) that creates a dysfunctional Ig receptor complex during B cell differentiation. Our results show that the lambda1(s) defect impairs the development of mature B cells when the H3-mu transgene insert is present in the hemizygous state. This suggests that the Gly --> Val substitution present in the C(lambda)1(s) chain at position 155 is sufficient to abrogate the selection of the H3/lambda1 pair. Unexpectedly, when the H3-mu transgene array is present in a homozygous state in lambda1(s) mice but not in 'wild-type' lambda1 mice (lambda1(+)), a significant number of mature B cells expressing all H3/lambda combinations can be developed. These results indicate that the overriding H3/lambda1 dominance observed in lambda1(+) mice is due to a positive selection process and not to a negative selection of other H3/lambda combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the mu chain.

Amino Acid Substitution↗
PubMed2000

Stenotrophomonas maltophilia D457R contains a cluster of genes from gram-positive bacteria involved in antibiotic and heavy metal resistance.

A cluster of genes involved in antibiotic and heavy metal resistance has been characterized from a clinical isolate of the gram-negative bacterium Stenotrophomonas maltophilia. These genes include a macrolide phosphotransferase (mphBM) and a cadmium efflux determinant (cadA), together with the gene cadC coding for its transcriptional regulator. The cadC cadA region is flanked by a truncated IS257 sequence and a region coding for a bin3 invertase. Despite their presence in a gram-negative bacterium, these genetic elements share a common gram-positive origin. The possible origin of these determinants as a remnant composite transposon as well as the role of gene transfer between gram-positive and gram-negative bacteria for the acquisition of antibiotic resistance determinants in chronic, mixed infections is discussed.

Anti-Bacterial Agents↗
PubMed2000

Epidemiologic tools for malaria surveillance in an urban setting of low endemicity along the Colombian Pacific coast.

An evaluation of 3 different methods for malaria diagnosis was carried out in an urban area of low endemicity on the Pacific coast of Colombia. Samples were collected from 833 symptomatic patients at a malaria clinic and examined by the polymerase chain reaction (PCR), quantitative buffy coat (QBC; Becton Dickinson, Franklin Lakes, NJ) method, and the traditional thick blood smear. The prevalence of Plasmodium falciparum malaria was 5.88% by thick blood smear, 7.34% by the QBC method, and 21.87% by PCR. The agreement between microscopists was 99.5%. The agreement between the QBC method and thick blood smear was 96.13% (n = 745). Samples positive by PCR but negative by thick blood smear or conversely negative by PCR and positive by thick blood smear were usually of low-level parasitemias. All 3 methods showed agreement in 76.3% of the samples. Sixty-nine (18.8%) samples were positive by PCR but negative by the other 2 methods. Ten samples were positive by both the QBC method and thick blood smear but negative by PCR; most of them had low-level parasitemias. The use of malaria diagnostic methods for epidemiologic surveillance is discussed.

Animals↗
PubMed2000

Prostate brachytherapy--the community hospital experience.

One of the options for treating localized carcinoma of the prostate includes the implantation of radioactive seeds under ultrasound guidance (brachytherapy). A community hospital-based prostate brachytherapy program was started in 1992. The overall survival and disease-free survival figures for the initial 100 patients treated in this program seem comparable to patients treated by radical prostatectomy or brachytherapy in larger series. The main side effects of brachytherapy included nocturia, daytime urinary frequency, dysuria, and proctitis. These side effects were transient and decreased to less than 10% by 12 to 24 months following implantation. Prostate brachytherapy can be effectively and safely provided in a community hospital setting.

Adenocarcinoma↗
PubMed1999

The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation.

The two members of the atypical protein kinase C (aPKC) subfamily of isozymes (zetaPKC and lambda/iotaPKC) are involved in the control of nuclear factor kappaB (NF-kappaB) through IKKbeta activation. Here we show that the previously described aPKC-binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo. p62 bridges the aPKCs to RIP, whereas the aPKCs link IKKbeta to p62. In this way, a signaling cascade of interactions is established from the TNF-R1 involving TRADD/RIP/p62/aPKCs/IKKbeta. These observations define a novel pathway for the activation of NF-kappaB involving the aPKCs and p62. Consistent with this model, the expression of a dominant-negative mutant lambda/iotaPKC impairs RIP-stimulated NF-kappaB activation. In addition, the expression of either an N-terminal aPKC-binding domain of p62, or its C-terminal RIP-binding region are sufficient to block NF-kappaB activation. Furthermore, transfection of an antisense construct of p62 severely abrogates NF-kappaB activation. Together, these results demonstrate that the interaction of p62 with RIP serves to link the atypical PKCs to the activation of NF-kappaB by the TNFalpha signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Echocardiographic evaluation in patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Cardiovascular abnormalities have been considered important extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD). However, little is known about their prevalence in patients with ADPKD undergoing hemodialysis (HD). To investigate whether cardiac abnormalities are more prevalent in these patients, clinical and echocardiographic manifestations of cardiovascular disease were evaluated in a group of 32 patients with ADPKD and a matched control group of 32 patients without diabetes treated by chronic HD for more than 6 months. Predialysis systolic and diastolic blood pressure (BP), prevalence of hypertension, and number of patients requiring antihypertensive medications were lower in the ADPKD group than controls. There was no difference in the prevalence of cardiac events, including cardiac failure, ischemic heart disease, and arrhythmia. Systolic dysfunction, diastolic patterns, and left ventricular hypertrophy were similar in the two groups. In patients with ADPKD, simple regression analysis showed left ventricular mass (LVM) index was correlated with hemoglobin level and predialytic systolic and diastolic BPs. In multiple regression analysis, predialysis systolic BP was the only independent variable linked to LVM index. The prevalence of aortic, mitral, and tricuspid valve disease did not differ between groups. In conclusion, the occurrence of cardiovascular complications in patients with ADPKD is similar to that of HD patients with other primary renal diseases, although hypertension is less prevalent.

Aged↗