Biomedical subjects

A Garcia

Publications and source records attributed to A Garcia.

At least 19 recordsLinked to original sources

PubMed2006

Efficacy of high doses of levofloxacin in experimental foreign-body infection by methicillin-susceptible Staphylococcus aureus.

Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic- and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: -1.24, -2.26, -2.1, -1.56, -1.47, -1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.

Acetamides↗

PubMed2006

Body weight, early growth and antler size influence antler bone mineral composition of Iberian red deer (Cervus elaphus hispanicus).

Researchers have devoted little attention to the possibility that the chemical composition of bone might be variable under normal nutrition conditions. This study assessed antler bone composition of 25 one-year old deer (spikes). Antler content of ash, Ca, P, K, Na, Mg, Fe and Zn was assessed in base and tine, and the mean composition or the difference in composition between tine and base was used to explain variability in antler length, weight and perimeter. In turn, mean composition and difference in concentration of each mineral were related to body measures at 1 year of age, weight at birth, weight at 1 year of age and weight gains during lactation, or between weaning and year of age. Chemical composition differed between base and tine in ash, Ca, P, K, Zn and Fe, but not in Na or Mg. Composition explained a mean variability of 77% in antler length and weight. Body weight and size, in turn, influenced mineral composition. The greatest body effect was that of gains during lactation on principal components analysis factor related to Ca, P and other major minerals such as Na, K or Mg. Antler bone composition is variable in normal conditions and such variability may play a role in biomechanical properties of the antler, but it is also likely to show the nutritional status or physiological effort to grow antlers. Assessing bone composition may emerge as a new useful tool to obtain information regarding bone biology and its bearer in other species including ours.

Animals↗

PubMed2006

Aparasitemic serological suspects in Trypanosoma brucei gambiense human African trypanosomiasis: a potential human reservoir of parasites?

The serological and parasitological tests used for Trypanosoma brucei gambiense human African trypanosomiasis (HAT) diagnosis have low specificity and sensitivity, respectively, and in the field, control program teams are faced with subjects with positive serology but negative parasitology who remain untreated. The aim of this work was to explore, using PCR tool, the significance of these aparasitemic serological suspects. Since discordant PCR results have been observed earlier with different extraction methods, two DNA extraction methods were compared (the Chelex 100 resin and the DNeasy Tissue kit). The study was conducted on 604 blood samples: 574 from parasitologically confirmed patients, aparasitemic serological suspects and endemic controls collected in Côte d'Ivoire and 30 from healthy volunteers collected in France. No significant differences were observed between the PCR results obtained with the two extraction methods. Concerning PCR, problems of reproducibility and discordances with both serological and parasitological test results were observed, mainly for the aparasitemic serological suspects. In addition to previous results that pointed to the existence of non-virulent or non-pathogenic trypanosome strains and of individual susceptibility leading to long term seropositivity without detectable parasitaemia but positive PCR, the results of this study support the notion of a long lasting human reservoir that may contribute to the maintenance or periodic resurgences of HAT in endemic foci.

Agglutination Tests↗

PubMed2006

Paramagnetic particles and mixing in micro-scale flows.

Mixing in microscale flows with rotating chains of paramagnetic particles can be enhanced by adjusting the ratio of viscous to magnetic forces so that chains dynamically break and reform. Lattice Boltzmann (LB) simulations were used to calculate the interaction between the fluid and suspended paramagnetic particles under the influence of a rotating magnetic field. Fluid velocities obtained from the LB simulations are used to solve the advection diffusion equation for massless tracer particles. At relatively high Mason numbers, small chains result in low edge velocities, and hence mixing is slower than at other Mason numbers. At low Mason numbers, long, stable chains form and produce little mixing toward the center of the chains. A peak in mixing rate is observed when chains break and reform. The uniformity of mixing is greater at higher Mason numbers because more small chains result in a larger number of small mixing areas.

Algorithms↗

PubMed2006

Renal donor implication in the origin of BK infection: analysis of genomic viral subtypes.

UNLABELLED: BK virus (BKV) reactivation in immunocompromised kidney transplant patients can produce a tubulointerstitial nephropathy (BKVN). Molecular tools that test for DNA-BKV provide early detection and assist in management, but some aspects of the pathogenesis of this infection, such as donor causality, remain unclear. MATERIALS AND METHODS: Between November 2004 and January 2006, 55 Spanish kidney donors were studied for BK infection. A quantitative PCR assay was performed on urine and serum to detect BKV. To determine the origin of the viral infection, a transcription control region of the BK polymorphism sequence was designed to identify the viral subtype. RESULTS: Fifteen of 55 (27%) donors were BK-PCR positive: 13 in urine and 2 in serum and urine. Moreover, monitoring of recipient pairs detected BK-PCR positivity in 14 of 73 recipients. We studied eight BK-PCR positive recipients (corresponding to four pairs) and their respective donors. The same viral genome was observed in the four pairs, namely, the A250-1-a, WW-like, AS, and JL genotypes. Interestingly, one of the four pairs showed the donor and the two recipients to display exactly the same JL genotype. CONCLUSION: On the basis of our preliminary results analyzing the molecular fingerprints of donor and recipient pairs, we have presented new data implicating the donor, in at least some cases, as the source of BK infection.

BK Virus↗

PubMed2006

Low malaria morbidity in a cohort of Senegalese children with free access to health structures.

We report the impact of the free access to health facilities on malaria morbidity in children from two to 15 years old, during a malaria transmission season in Niakhar, Senegal. Between July and December 2002, 227 malaria attacks occured in 566 children. Only one case of severe malaria was observed and no death has been reported. Our results demonstrate furthermore that easier access to health facilities and to early treatment is playing a key role in malaria control.

Adolescent↗

PubMed2006

Optimal dose and timing in phytohaemagglutinin skin-testing of deer.

AIM: To establish the optimal dose of the mitogen phytohaemagglutinin (PHA) and the optimal time for measuring increased skin-fold thickness in red deer following intradermal injection, as an indicator of cell-mediated immune response. METHODS: Three doses (10, 50 and 250 microg) of PHA were injected intradermally in the right side of the neck, and phosphate buffered saline (PBS) was injected at a fourth site as a control, in 20 captive Iberian red deer (Cervus elaphus hispanicus) hinds. Skin-fold thicknesses were measured at 0, 12, 24, 36, 48, 60, 72, 84 and 96 h following injection. RESULTS: The highest dose of PHA tested (250 microg) resulted in a clear and long-lasting cellular response; increases in skin-fold thickness between 48 and 84 h post-injection varied minimally and response correlated positively with liveweight. No correlations with liveweight and no clear increases in skin-fold thickness occurred at the lower doses of PHA or the PBS. CONCLUSIONS AND CLINICAL RELEVANCE: This technique could be applied with minimal training and without specialised equipment in deer, for immunological and ecological research.

Animals↗

PubMed2006

[The impact of war on the evolution of sleeping sickness in west-central Côte d'Ivoire].

OBJECTIVE: To evaluate the situation of sleeping sickness in west-central Côte d'Ivoire from 2000 to 2003, in view of the war which broke out in September 2002. METHODS: Active surveys by medical teams and passive case detection. RESULTS: Between 2000 and 2003, 250 patients were diagnosed with sleeping sickness. At first it appeared that sleeping sickness prevalence had fallen since the beginning of political troubles. But this apparent drop was due to poor population coverage. Participation in medical surveys differed according to ethnic group, reflecting land use conflicts between ethnic communities. Such conflicts are common in this area, but have been exacerbated by the war. CONCLUSION: In war, assessing the importance of sleeping sickness by medical surveys only is very difficult. But detection of sleeping sickness cases by passive surveillance increased.

Conflict, Psychological↗

PubMed2006

P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation.

BACKGROUND: Thromboxane A2 (TXA2) is a positive feedback lipid mediator that is generated upon stimulation of platelets with various agonists. Aspirin works as an antithrombotic drug by blocking the generation of TXA2. The aim of this study was to evaluate the role of the purinergic P2Y receptors in thrombin-induced TXA2 generation. RESULTS: PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin, induced the activation of cytosolic phospholipase A2 (cPLA2), release of arachidonic acid (AA) from membrane-bound phospholipids, and subsequent TXA2 generation in human platelets. The actions of these agonists were significantly inhibited in the presence of the P2Y12 receptor antagonist, AR-C69931MX, but not the P2Y1 receptor antagonist, MRS2179. In addition, AYPGKF- and thrombin-induced TXA2 generation was significantly reduced in platelets from mice dosed with clopidogrel, confirming the results obtained with the human platelets. Also, Pearl mouse platelets that lack releasable nucleotides generated significantly less TXA2 when compared with the wild-type littermates in response to PAR stimulation. Inhibition of extracellular signal-regulated protein kinase 1/2 (Erk 1/2) activation using U0126, an inhibitor of MAP kinase kinase (MEK), suppressed PAR-mediated cPLA2 phosphorylation and TXA2 generation. Further, platelets that were pretreated with AR-C69931MX, as well as Pearl mouse platelets, displayed the reduced levels of Erk1/2 phosphorylation upon stimulation with the PAR agonists. CONCLUSIONS: Based on these findings, we conclude that thrombin-induced Erk1/2 activation is essential for PAR-mediated TXA2 generation, which is potentiated by the P2Y12 receptor-mediated signaling pathway but not the P2Y1 receptor-mediated signaling pathway. Finally, using selective inhibitors of Src kinases, we show that PAR-mediated Src activation precedes Erk1/2 activation.

Adenosine Monophosphate↗

PubMed2006

Prevalence of high risk human papillomavirus types among Nicaraguan women with histological proved pre-neoplastic and neoplastic lesions of the cervix.

OBJECTIVES: To determine the prevalence of high risk human papillomavirus (HPV) types in Nicaraguan women with histological proved pre-neoplastic and neoplastic cervical lesions, and to assess its potential impact on preventive strategies. METHODS: 206 women with histopathological confirmed cervical lesions (CIN I or worse) were screened for HPV DNA on a liquid based cytology sample, using an HPV short fragment polymerase chain reaction based assay. HPV positive samples were genotyped with a reverse hybridisation line probe assay (Lipa). HPV negative samples were re-analysed using type specific real time polymerase chain reaction. RESULTS: Of all lesions CIN II or worse, 12% tested negative. Prevalence of high risk HPV increased from 48.1% in cervical intraepithelial neoplasia I (CIN I) to 94.7% in invasive squamous cervical carcinoma (SCC). The most prevalent high risk HPV types were, in order of prevalence rate, HPV 16, 58, 31 and 52. HPV 16 and/or HPV 31 were present in 63.2% of SCC cases. CONCLUSION: Targeting HPV 16 and 31 with prophylactic vaccines could possibly have an important impact on the incidence of invasive cervical carcinoma in Nicaragua. Further research is needed to define the oncogenic potential of other high prevalent HPV genotypes. Meanwhile, primary prevention and cervical cancer screening programmes should be optimised.

Adolescent↗

PubMed2006

Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors.

A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.

Carcinoma, Endometrioid↗

PubMed2006

Seasonal and lactational changes in mineral composition of milk from Iberian red deer (Cervus elaphus hispanicus).

Milk minerals are important for calf growth, and they have other roles as well, such as immune regulation. This 2-yr study examined content of Ca, P, Mg, Na, K, Fe, and Zn in milk of 54 Iberian red deer hinds through 18 wk of lactation. Mean mineral composition of fresh milk was ash = 1.168 +/- 0.007%, Ca = 2,330 +/- 20 mg/kg, P = 640 +/- 10 mg/kg, K = 1,100 +/- 10 mg/kg, Na = 385 +/- 3 mg/kg, Mg = 138 +/- 1 mg/kg, Zn = 12.5 +/- 0.2 mg/kg, and Fe = 0.65 +/- 0.03 mg/kg. All minerals except Mg varied by week of lactation, but variation was usually <10% except for Fe (83% variation) and Zn (30% variation); both of those minerals increased as lactation proceeded. Increased concentrations of Fe and Zn in later lactation compensated for the reduction in milk production in mid and late lactation such that daily production was less variable for Fe (55% variation) or Zn (79% variation) than for other minerals (118 to 135% variation). Potassium content of milk decreased across time, but that effect occurred primarily during the last few weeks of lactation. Calving later vs. early in the calving season had variable effects on concentrations of different minerals: P, Mg, and K concentrations were not affected; Ca, Mg, and Na were all lower in milk from later calving hinds; and both Fe and Zn had higher concentrations in milk from hinds that calved later in the season. Lactating hinds seem to maintain a more stable daily yield of the microminerals Fe and Zn in milk compared with more variable concentrations of macrominerals as lactation progresses. Because of the essential role of Fe and Zn in immune function, a more stable supply of those minerals might be important to the health of growing red deer calves.

Animals↗

PubMed2005

Multiple pulmonary neoplasia positive for thyroglobulin.

We present, for the first time, a case of carcinoid metastatic pulmonary tumor positive for thyroglobulin. A 73-yr-old woman diagnosed with metastases of probable thyroid carcinoma, manifested by a mediastinic mass and multiple pulmonary nodules positive for radioiodine (I131). Histological analysis showed typical findings of carcinoid tumor with positive immunohistochemistry for neuron-specific enolase, synaptophysin and thyroglobulin, and negative for chromogranin and calcitonin. We underline the exceptional finding of positive reaction for thyroglobulin, and discuss difficulties in differential diagnosis between metastatic differentiated thyroid and carcinoid neoplasms.

Aged↗

PubMed2005

Effect of parathyroidectomy on renal graft function.

Some authors have reported acute impairment of renal transplant function after parathyroidectomy (PTx). Since 1996 PTx has been performed in 22 renal transplant recipients (follow-up, 24.2 +/- 15 months; serum creatinine concentration (SCr) pre-PTx, 1.26 +/- 0.4 mg/dL). We analyzed the serum levels of immunoreactive parathyroid hormone, calcitriol, calcium, phosphate, alkaline phosphatase, SCr, and hemoglobin, as well as proteinuria, blood pressure, and immunosuppressive treatment at several times: before PTx and at 7 days, 1 month, and then every 3 months post-PTx. After PTx we observed acute renal function deterioration until the third post-PTx month, when SCr levels returned to baseline values. We found no changes in blood pressure, although there was a trend toward a reduced dosage of antihypertensive drugs. We compared the patients who showed more significant increases (>30% from baseline) in SCr (group A, n = 7) with those who did not (group B, n = 15). Group A had higher SCr levels pre-PTx. We observed no other significant differences, either pre-PTx or post-PTx. In 2 patients in group A, SCr returned to baseline at the third month after PTx, but in the other 5 the renal function impairment persisted. Taking into account this risk and that severe hyperparathyroidism does not revert after transplantation, it would seem more appropriate in such cases to perform PTx while the patient is on the waiting list. The causes of this renal functional impairment are not clear, but the patients who showed worse deterioration also had a worse renal function pre-PTx.

Antihypertensive Agents↗

PubMed2005

Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection.

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.

Adenine↗

PubMed2005

Changes in the digestible lysine and sulfur amino acid needs of broiler chicks during the first three weeks posthatching.

Four experiments were conducted to study the changes in the digestible lysine (DLYS) and sulfur amino acid (DSAA) requirements of broilers during the first 21 d posthatching. Cobb 500 by-product male broilers were fed corn-corn gluten meal-soybean meal diets formulated to be isocaloric and isonitrogenous. Five graded levels of either Lys or SAA were used, varying from 0.78 to 1.28% DLYS (experiments 1 and 2) and from 0.61 to 1.08% DSAA (experiments 3 and 4). Body weight gain (BWG) and gain:feed ratio (GF) were calculated at 4, 7, and 21 d. The DLYS requirements based on BWG varied from 0.98 at 4 d of age to 1.01% at 21 d in experiment 1 and from 0.95 at 4 d of age to 0.99% at 21 d, in experiment 2. Based on GF, the DLYS requirement varied from 1.08 to 1.10% in experiment 1, and from 0.98 to 0.94% in experiment 2 at 4 and 21 d, respectively. The estimated DSAA requirements for BWG varied from 0.83 to 0.88% or from 0.71 to 0.75% for 4 and 21 d in experiments 3 and 4, respectively. For GF, the DSAA decreased slightly from 0.88% at 4 d to 0.83% at 21 d in experiment 3, but did not change in experiment 4 (0.81%). Minimal changes in the DLYS or DSAA estimated requirements occurred during the first 21 d of age, which suggests that the recommended DLYS and DSAA levels determined at 21 d of age appear to be adequate to meet chick needs for the first week of age.

Amino Acids, Sulfur↗

PubMed2005

Risk factors associated with house infestation by the Chagas disease vector Triatoma pallidipennis in Cuernavaca metropolitan area, Mexico.

Chagas disease caused by infection with Trypanosoma cruzi Chagas (Kinetoplastida: Trypanosomatidae) is widespread in Mexico, transmitted by various triatomine bugs (Hemiptera: Reduviidae). The only domestic vector in Cuernavaca (population 650 000) is Triatoma pallidipennis (Ståhl) with T. cruzi seroprevalence ranging from 1% to 9% in the resident human population. We surveyed possible risk factors for T. pallidipennis infestation at Cuernavaca (altitude 1200-2200 m) on south-western slopes of the Sierra Madre Occidental. This metropolitan area (with five administrative counties) has rapid urbanization, forested environs and proliferation of 'weekend housing' for visitors from Mexico City, 60 km to the north. To assess factors associated with T. pallidipennis infestation, we first stratified Cuernavaca by altitude and by socio-economic status of population catchment units (PCUs). Within each PCU, one to three blocks were chosen for cluster sampling (three houses/block) and information about Chagas disease was distributed. After obtaining signed consent from householders, representative houses were routinely and opportunistically inspected for T. pallidipennis and surveyed for demographic, economic, physical and other potential risk factors. Of the 1129 houses assessed, T. pallidipennis was found in 4.1% (range 3.0-6.8% per county) and the T. cruzi infection rate was approximately 50% in bugs. Rates of house infestation in poor PCUs were double those in higher socio-economic strata (odds ratio 2.12, confidence interval 1.03-4.3), with >4-fold greater crowding index of T. pallidipennis. The bug density index was inversely correlated with PCU altitude and socio-economic category (altitude of homes being associated with prosperity), while the bug colonization index (presence of nymphs indicating breeding) did not vary significantly across the PCU categories, but did vary according to altitude. Multivariate regression analysis showed that the most significant risk factors associated with T. pallidipennis infestation were lower altitude (linked with lower socio-economic status), garden area >80 m(2), dogs at liberty to enter the house, occurrence of squirrels and opossums around the house, presence of pigs in the surrounding area and having at least one of the adjacent lots empty (unconstructed). Householders who had received information about Chagas disease comprised 33% from infested houses (14/42) but only 15% from non-infested houses (148/984). Hence, the awareness of Chagas disease was significantly associated with having a bug-free house (P < 0.01). When shown specimens of T. pallidipennis, the proportions of householders who recognized them were 78% from infested houses but only 29% of those with uninfested houses. Given the low infestation rates and the high capacity of the population to act appropriately once they have received information regarding this disease and its vector, relevant health education is expected to have a significant impact on triatomine control in this metropolitan area.

Altitude↗

PubMed2005

Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb.

The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system to create conditional, heart-specific Rb-deficient mice. Mice that are deficient in Rb exclusively in cardiac myocytes (CRbL/L) are born with the expected Mendelian distribution, and the adult mice displayed no change in heart size, myocyte cell cycle distribution, myocyte apoptosis, or mechanical function. Since both Rb and p130 are expressed in the adult myocardium, we created double-knockout mice (CRbL/L p130-/-) to determine it these proteins have a shared role in regulating cardiac myocyte cell cycle progression. Adult CRbL/L p130-/- mice demonstrated a threefold increase in the heart weight-to-body weight ratio and showed increased numbers of bromodeoxyuridine- and phosphorylated histone H3-positive nuclei, consistent with persistent myocyte cycling. Likewise, the combined deletion of Rb plus p130 up-regulated myocardial expression of Myc, E2F-1, and G1 cyclin-dependent kinase activities, synergistically. Thus, Rb and p130 have overlapping functional roles in vivo to suppress cell cycle activators, including Myc, and maintain quiescence in postnatal cardiac muscle.

Animals↗