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Biomedical subjects

E Garcia

Publications and source records attributed to E Garcia.

At least 19 recordsLinked to original sources

Catch-up growth follows an abnormal pattern in experimental renal insufficiency and growth hormone treatment normalizes it.

The primary goal of this study was to determine if the ability to undergo catch-up growth following a transient injury is preserved in an experimental model of moderate chronic renal failure (CRF) and the effect of growth hormone (GH) administration on such phenomenon. Young rats were subtotally nephrectomized (days 0 and 4) (Nx). From days 11 to 13, food intake was restricted in subgroups of Nx and control (C) rats (NxR and CR). After refeeding, subgroups of NxR and CR rats received GH from days 14 to 20 (NxRGH and CRGH). Rats were killed on days 14 (C, CR, Nx, NxR), 17 and 21 (C, CR, CRGH, Nx, NxR, NxRGH), and 36 (C, CR, Nx, NxR). Longitudinal growth rate was measured by osseous front advance in the proximal tibiae. With refeeding, growth rate of CR, NxR, and NXrGH rats became significantly greater than that of C, indicating catch-up growth. This occurred later and with lower growth rate in NxR than in CR rats, whereas the characteristics of catch-up growth in CR and NxRGH animals were similar. Changes in growth rate were associated with modifications in the morphology and proliferative activity of growth cartilage. We conclude that catch-up growth occurs in renal insufficiency but follows a different pattern from that observed with normal renal function. GH treatment normalizes the pattern of catch-up growth in CRF. Changes in growth velocity are associated to modifications in the structure and dynamics of growth cartilage.

Animals↗

Effect of food intake on the bioavailability of almotriptan, an antimigraine compound, in healthy volunteers: an open, randomized, crossover, single-dose clinical trial.

This open, randomized, crossover, single-dose clinical trial evaluated the possible pharmacokinetic interaction between a single oral dose of almotriptan 25 mg, a 5-HT1B/1D receptor agonist for the acute treatment of migraine, and food intake in healthy volunteers. The influence of food intake in the rate and extent of almotriptan absorption was evaluated by bioequivalence criteria. Tolerability and safety of treatment were also assessed. 16 healthy volunteers (8 men and 8 women, aged 19-27 years) received a crossed single oral dose of almotriptan 25 mg under fasting and fed conditions, separated by a 7-day washout period. The treatment given under fasting condition was considered as reference. Plasma levels of almotriptan were analyzed using high-performance liquid chromatography (HPLC) and UV detection at 227 nm. The 90% confidence intervals (CI) for the logarithmically transformed Cmax and AUC0-infinity, values of almotriptan under fasting and fed conditions (97.8 - 124% and 102.9 - 108.2%, respectively) fell into the predetermined accepted range of 80 - 125%. No statistically significant differences in Cmax, tmax, AUC0-infinity, MRT and t1/2 were observed under fasting and fed conditions between men and women. Tolerability of treatments was good throughout the whole study period. In conclusion, administration of almotriptan 25 mg is bioequivalent under fasting and fed conditions in healthy men and women. Therefore, it is unlikely that concomitant food intake would produce clinially relevant differences in therapeutic effect with almotriptan at the dose studied here.

Administration, Oral↗

Development of an ecosystem sensitivity model regarding mercury levels in fish using a preference modeling methodology: application to the Canadian boreal system.

The objective of this study is to use a preference modeling methodology as a predictive tool to roughly assess the sensitivity of the ecosystems regarding mercury (Hg) concentrations in fish. We apply a preference modeling methodology to rank lakes within the boreal forest from highest to lowest Hg concentrations in fish using simple environmental factors. Among the numerous variables influencing Hg fate in the environment, we only retain simple key indicators that are expected to influence Hg concentrations in fish tissue such as watershed characteristics of the lake (percentage of the catchment area of the lake, ratio of drainage area versus lake area, percentage of the drainage area of the lake as wetlands, land use, and clear-cutting), lake characteristics (chlorophyll, dissolved organic carbon, pH, and fishing intensity), and atmospheric Hg inputs. Preliminary results of modeling that we carried out using a set of Canadian lakes of boreal forest data are promising. With only a minimum set of criteria, we are able to reproduce the trends of Hg contamination in fish caught in six regions of the Canadian boreal forest and classify the sensitivity of the ecosystems to Hg loadings in three categories: high, medium, and low.

Animals↗

Adaptive tele-application for remote neurology diagnosis.

This paper presents the Collaborative Tele-Neurology (TeNeCi) project which allows practitioners to use telecommunication technologies to provide medical information and services for neurological diseases. Specificities of remote neurology are described and the Cooperative Application Framework (CAliF) multimedia platform on which TeNeCi relies is presented. The technical requirements of such a project in terms of communication and consistency management, audio and video transmissions, and network support, as well as implementation of TeNeCi was evaluated. The software used in this application is composed of several services, such as a Digital Imaging and Communications in Medicine (DICOM) explorer, a DICOM viewer, and a security service. Tests performed on this first TeNeCi release showed good results, and allowed us to explore a larger collaborative experimentation between hospitals in France and Switzerland.

Emergency Medical Services↗

Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties.

One of the main difficulties with primary rat brain endothelial cell (RBEC) cultures is obtaining pure cultures. The variation in purity limits the achievement of in vitro models of the rat blood-brain barrier. As P-glycoprotein expression is known to be much higher in RBECs than in any contaminating cells, we have tested the effect of five P-glycoprotein substrates (vincristine, vinblastine, colchicine, puromycin and doxorubicin) on RBEC cultures, assuming that RBECs would resist the treatment with these toxic compounds whereas contaminating cells would not. Treatment with either 4 microg/mL puromycin for the first 2 days of culture or 3 microg/mL puromycin for the first 3 days showed the best results without causing toxicity to the cells. Transendothelial electrical resistance was significantly increased in cell monolayers treated with puromycin compared with untreated cell monolayers. When cocultured with astrocytes in the presence of cAMP, the puromycin-treated RBEC monolayer showed a highly reduced permeability to sodium fluorescein (down to 0.75 x 10(-6) cm/s) and a high electrical resistance (up to 500 Omega x cm(2)). In conclusion, this method of RBEC purification will allow the production of in vitro models of the rat blood-brain barrier for cellular and molecular biology studies as well as pharmacological investigations.

Animals↗

Tuberculosis skin testing, anergy and protein malnutrition in Peru.

SETTING: Malnutrition and intestinal parasites cause immunosuppression. This may cause false-negative tuberculin skin tests (TST) and failure to identify tuberculosis (TB) infection. OBJECTIVE: To assess factors associated with TST positivity and anergy in disadvantaged communities in Peru. DESIGN: A study of 212 randomly selected adults: 102 in a rural Amazonian village and 110 shanty town residents in urban Lima. RESULTS: Respectively 52% and 53% of urban and rural jungle populations were TST-positive. Using simultaneous tetanus and candida skin tests, 99% had at least one positive skin test. Generalised anergy was therefore rare, despite frequent intestinal parasitic infection, including 34% helminth infection prevalence in the jungle. TST positivity was associated with age (P = 0.001), known TB contact (P = 0.02) and poor household ventilation (P = 0.007). TST positivity was not significantly associated with crowding, reported past TB, single/multiple BCG vaccination, income, intestinal parasites, dietary factors, body mass index or body fat. Individuals with lower anthropometric body protein, as measured by corrected arm muscle area, were less likely to be TST-positive (P = 0.02), implying that protein malnutrition caused tuberculin-specific anergy. CONCLUSION: These results identify the importance of household ventilation for community TB transmission and add to the evidence that protein malnutrition suppresses TB immunity, causing false-negative TST results.

Adolescent↗

Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis.

Yersinia pestis, the causative agent of plague, is a highly uniform clone that diverged recently from the enteric pathogen Yersinia pseudotuberculosis. Despite their close genetic relationship, they differ radically in their pathogenicity and transmission. Here, we report the complete genomic sequence of Y. pseudotuberculosis IP32953 and its use for detailed genome comparisons with available Y. pestis sequences. Analyses of identified differences across a panel of Yersinia isolates from around the world reveal 32 Y. pestis chromosomal genes that, together with the two Y. pestis-specific plasmids, to our knowledge, represent the only new genetic material in Y. pestis acquired since the the divergence from Y. pseudotuberculosis. In contrast, 149 other pseudogenes (doubling the previous estimate) and 317 genes absent from Y. pestis were detected, indicating that as many as 13% of Y. pseudotuberculosis genes no longer function in Y. pestis. Extensive insertion sequence-mediated genome rearrangements and reductive evolution through massive gene loss, resulting in elimination and modification of preexisting gene expression pathways, appear to be more important than acquisition of genes in the evolution of Y. pestis. These results provide a sobering example of how a highly virulent epidemic clone can suddenly emerge from a less virulent, closely related progenitor.

Bacteriophages↗

Neurocysticercosis: relationship between the developmental stage of metacestode present and the titre of specific IgG in the cerebrospinal fluid.

In double-blind, immunological assays, samples of cerebrospinal fluid (CSF) from 141 patients with neurocysticercosis (NCC) or other neurological disorders were tested for IgG reacting with the excretory/secretory (E/S) antigens of Taenia solium metacestodes. The results for the cases of NCC were then correlated with the developmental stage of the metacestodes present in each case, as assessed by computerized tomography and magnetic-resonance imaging. In the ELISA first used, the samples of CSF from most (88%) of the patients with the vesicular stage of NCC (some of whom also had the degenerate and/or calcified metacestodes) were found to contain the specific IgG. In electro-immunotransfer blot (EITB) assays, three of the E/S antigens, of 95, 49 and 29 kDA, were recognized by 86%-100% of the ELISA-positive CSF. When these three antigens were isolated and tested, as a pool, against all the CSF samples in double-blind ELISA, almost all (96.6%) of the CSF samples from patients with metacestodes at the vesicular stage were recognized. In the detection of individuals with vesicular metacestodes, the assay based on the three isolated antigens was significantly more sensitive than that based on the crude extract of E/S antigens (P < 0.05). In EITB assays based on the three antigens, the isolated proteins were again recognized by IgG in the CSF samples from those with vesicular metacestodes, but without the background 'noise' seen with the crude extract. In every assay employed, none of the CSF samples from NCC cases who only harboured degenerative and/or calcified metacestodes and none of those from patients who had other neurological disorders gave a positive result. The use in ELISA and EITB of antigens purified from crude extracts of metacestode E/S proteins could improve the immunodiagnosis of the vesicular stage of NCC, and allow better evaluation of NCC cases both pre- and post-treatment.

Animals↗

Novel virulence-associated type II secretion system unique to high-pathogenicity Yersinia enterocolitica.

Yersinia enterocolitica strains comprise an important group of bacterial enteropathogens that cause a broad range of gastrointestinal syndromes. Three groups are distinguishable within this bacterial species, namely, the nonpathogenic group (biotype 1A strains), the low-pathogenicity, non-mouse-lethal group (biotypes 2 to 5), and the high-pathogenicity, mouse-lethal group (biotype 1B). To date, the presence of the high-pathogenicity island (HPI), a chromosomal locus that encodes the yersiniabactin system (involved in iron uptake), defines essentially the difference between low-pathogenicity and high-pathogenicity Y. enterocolitica strains, with the low-pathogenicity strains lacking the HPI. Using the powerful tool of representational difference analysis between the nonpathogenic 1A strain, NF-O, and its high-pathogenicity 1B counterpart, WA-314, we have identified a novel type II secretion gene cluster (yts1C-S) occurring exclusively in the high-pathogenicity group. The encoded secreton, designated Yts1 (for Yersinia type II secretion 1) was shown to be important for virulence in mice. A close examination of the almost completed genome sequence of another high-pathogenicity representative, Y. enterocolitica 8081, revealed a second putative type II secretion cluster uniformly distributed among all Y. enterocolitica isolates. This putative species-specific cluster (designated yts2) differed significantly from yts1, while resembling more closely the putative type II cluster present on the genome of Y. pestis. The Yts1 secreton thus appears to have been additionally acquired by the high-pathogenicity assemblage for a virulence-associated function.

Animals↗

A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine-induced skin reactivity.

OBJECTIVE: The aim of this double-blind, randomized, crossover, placebo-controlled clinical trial was to compare the inhibition of the histamine-induced skin reaction induced by ebastine 20 mg with respect to that induced by fexofenadine 120 mg or placebo. METHODS: Eighteen volunteers (10 males, 8 females) received the three treatments once daily for 5 days, with a mean 7-day washout period between treatments. Intradermal tests, using 0.05 ml from a solution containing 100 microg/ml of histamine, were performed at baseline and at 1, 1.5, 2, 3, 10 and 24 h after a single dose and repeated 5-day dose, and in addition after 34, 48, 58 and 72 h after repeated 5-day dose. RESULTS: After 24 h of acute administration, ebastine 20 mg was significantly more effective than fexofenadine 120 mg in reducing the wheal and flare induced by histamine challenge (p<0.001). Although fexofenadine 120 mg had the shortest onset of action (1.5 vs. 3 h in ebastine 20 mg), the duration of its antihistamine effect was the shortest (24 vs. 58 h in ebastine 20 mg) and wheal reduction after 24 h was not significantly different from placebo. The overall effect after single and repeated 5-day dose, expressed as the AUC of reduction of wheal and flare area (%/h), showed the following order of magnitude: ebastine 20 mg>fexofenadine 120 mg>placebo. No significant differences in the incidence of adverse events were found between the three treatments. CONCLUSIONS: The present results clearly show a superior and long-acting effect of ebastine 20 mg compared with fexofenadine 120 mg on the skin response to histamine 24 h after dosing.

Administration, Oral↗

Pseudorapidity and centrality dependence of the collective flow of charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV.

This paper describes the measurement of collective flow for charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The measured azimuthal hit anisotropy is presented over a wide range of pseudorapidity (-5.0<eta<5.3) for the first time at this energy. The result, averaged over momenta and particle species, is observed to reach 7% for peripheral collisions at midrapidity, falling off with centrality and increasing |eta|. These results call into question the common assumption of longitudinal boost invariance over a large region of rapidity in RHIC collisions.

Journal Article↗

Representational difference analysis uncovers a novel IS10-like insertion element unique to pathogenic strains of Yersinia enterocolitica.

The method of suppressive subtractive hybridization was employed to map out genomic differences between the highly pathogenic Yersinia enterocolitica (Ye) biogroup 1B, serotype O:8 strain (WA-314) and the closely related apathogenic Y. enterocolitica biogroup 1A, serotype O:5 strain (NF-O). A novel IS10-like element, IS1330, uncovered by this technique was found to be uniquely present in high copy numbers among the highly pathogenic Y. enterocolitica 1B strains, while a single copy of the element was found in the low pathogenic Ye biogroup 4 serotype O:3 strain. The 1321-bp repetitive element has 19-bp imperfect inverted terminal repeats and is bracketed by a 10-bp duplication of the target sequence. The predicted transposase shares high homology with the IS10 open reading frame of the large virulence plasmid pWR501, of Shigella flexneri, with IS10 transposase of Salmonella typhi, and with IS1999 (tnpA) of Pseudomonas aeruginosa. The IS1330 tnp gene is transcribed in vitro and in vivo in HeLa cells. At least one copy of IS1330 flanks the recently described chromosomal type III secretion cluster in Y. enterocolitica WA-314, O:8, and future studies should shed light on whether this novel transposase mediates transposition events in highly pathogenic Y. enterocolitica strains, thus enhancing the genetic plasticity of this species.

Base Sequence↗

Patient-controlled epidural fentanyl following spinal fentanyl at Caesarean section.

Spinal fentanyl can improve analgesia during Caesarean section. However, there is evidence that, following its relatively short-lived analgesic effect, there is a more prolonged spinal opioid tolerance effect. The effectiveness of postoperative epidural fentanyl analgesia may therefore be reduced following the use of spinal fentanyl at operation. This randomised, double-blind study was designed to assess whether patient-controlled epidural fentanyl could produce effective analgesia following 25 microg of spinal fentanyl at operation. Patients undergoing elective Caesarean section received spinal bupivacaine combined with either fentanyl 25 microg (fentanyl group; n = 18) or normal saline (saline group; n = 18). Patient-controlled epidural fentanyl was used for postoperative analgesia. The fentanyl group used a mean of 23.4 (SD 14.5) microg x h(-1) of fentanyl, compared with 27.0 (10.8) microg x h(-1) for the saline group (p =0.41). Using a 0-100 mm visual analogue score for pain, the maximum pain score recorded at rest for the fentanyl group was median 24 [IQR 15-35] mm, compared with 15 [13-45] mm for the saline group (p = 0.41). The maximum pain score recorded on coughing for the fentanyl group was 29 [24-46] mm, compared with 27 [19-47] mm for the saline group (p = 0.44). Nine of the fentanyl group rated postoperative analgesia as excellent and nine as good, compared with 10 of the saline group who rated it as excellent and eight as good (p = 0.74). Epidural fentanyl can produce effective analgesia following the use of 25 microg spinal fentanyl at Caesarean section.

Adult↗

Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.

AIMS: We examined the clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2 h), intermediate presentation (2-4 h), and late presentation (>or=4 h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5.8% in the angioplasty group vs 12.5% in the thrombolysis group, in patients with intermediate presentation, 8.6% vs 14.2%, respectively, and in patients presenting late 7.7% vs 19.4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. CONCLUSIONS: Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.

Adult↗

Development of a platinized and ferrocene-mediated cholesterol amperometric biosensor based on electropolymerization of polypyrrole in a flow system.

The preparation of a cholesterol amperometric biosensor using a platinized Pt electrode as a support for the electropolymerization of a polypyrrole film, in which cholesterol oxidase and ferrocene monocarboxylic acid (electron-transfer mediator) were co-entrapped, is described. All the biosensor preparation steps (platinization and electropolymerization) and the cholesterol determination take place in the same flow system. The presence of the mediator enhances the sensitivity and selectivity of the platinized biosensor without modifying the dynamic parameters of the response, and the platinized layer improves the operational lifetime of the mediated sensor. The sensitivity obtained was 88.51 nA mM(-1) and the limit of detection was 12.4 microM of cholesterol. The analytical properties of the biosensor for the flow-injection determination of cholesterol were studied and compared with those of other more simple amperometric biosensor configurations.

Biosensing Techniques↗

Energy dependence of particle multiplicities in central Au+Au collisions.

We present the first measurement of the pseudorapidity density of primary charged particles in Au+Au collisions at root square[s(NN)] = 200 GeV. For the 6% most central collisions, we obtain dN(ch)/d(eta)/(/eta/<1) = 650+/-35(syst). Compared to collisions at root square[s(NN)] = 130 GeV, the highest energy studied previously, an increase by a factor of 1.14+/-0.05 at 90% confidence level, is found. The energy dependence of the pseudorapidity density is discussed in comparison with data from proton-induced collisions and theoretical predictions.

Journal Article↗

Antilambda production in Au+Au collisions at 11.7A GeV/c.

We present results for antilambda and antiproton production in Au+Au collisions at 11.7 A GeV/c including spectra and extracted invariant yields for both species in central and peripheral collisions in the rapidity range 1.0<y<1.4. The antilambda yield increases from dN(Lambda;)/dy = 1.2(+0.7+0.2)(-0.6-0.2)x10(-3) in peripheral collisions to 19(+4+3)(-5-2)x10(-3) in central collisions. The direct antiproton yield is deduced from the measured total antiproton spectra to extract the ratio of antilambda-to-direct-antiproton production. The Lambda/p ratio near midrapidity increases from 0.26(+0.19+0.5)(-0.15-0.4) in peripheral collisions to 3.6(+4.7+2.7)(-1.8-1.1) in central collisions, a value larger than current theoretical estimates.

Journal Article↗