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Biomedical subjects

A Sierra

Publications and source records attributed to A Sierra.

At least 19 recordsLinked to original sources
PubMed2006

Changes in the epidemiology of meticillin-resistant Staphylococcus aureus associated with the emergence of EMRSA-16 at a university hospital.

This study investigated the molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in the University Hospital of the Canary Islands (HUC) in order to evaluate epidemiological changes over a six-year period. Clinical and epidemiological data were collected between May 2000 and December 2003, and isolates were subjected to pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), SCCmec typing and spa typing. Since 2000, the rate of MRSA infections has increased at the HUC, coinciding with the emergence and spread of the EMRSA-16 clone (ST36-MRSA-II) and replacement of the Iberian clone (ST247-MRSA-I). Genotypic changes were associated with changes in the epidemiological profile. The mean age and proportion of patients over 60 years old (P=0.01) and the proportion of respiratory infections (P=0.001) increased significantly. Gentamicin and tetracycline susceptibility of MRSA isolates increased (P<0.001) following the emergence of EMRSA-16. Combining PFGE, SCCmec and MLST has been instrumental in understanding these changes and defining the clones circulating in the HUC patient population.

Age Factors↗
PubMed2006

Antiproliferative and cytotoxic properties of bevacizumab on different ocular cells.

AIM: To evaluate the antiproliferative and cytotoxic properties of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), on human retinal pigment epithelium (ARPE19) cells, rat retinal ganglion cells (RGC5), and pig choroidal endothelial cells (CEC). METHODS: Monolayer cultures of ARPE19, RGC5, and CEC were used. Bevacizumab (0.008-2.5 mg/ml), diluted in culture medium, was added to cells that were growing on cell culture dishes. Cellular proliferative activity was monitored by 5'-bromo-2'-deoxyuridine (BrdU) incorporation into cellular DNA and the morphology assessed microscopically. For cytotoxicity assays ARPE19, RGC5, and CEC cells were grown to confluence and then cultured in a serum depleted medium to ensure a static milieu. The MTT test was performed after 1 day. The "Live/Dead" viability/cytotoxicity assay was performed and analysed by fluorescence microscopy after 6, 12, 18, 24, 30, 36, and 48 hours of incubation. Expression of VEGF, VEGF receptors (VEGFR1 and VEGFR2) and von Willebrand factor was analysed by immunohistochemistry. RESULTS: No cytotoxicity of bevacizumab on RGC5, CEC, and ARPE19 cells could be observed after 1 day. However, after 2 days at a bevacizumab concentration of 2.5 mg/ml a moderate decrease in ARPE19 cell numbers and cell viability was observed. Bevacizumab caused a dose dependent suppression of DNA synthesis in CEC as a result of a moderate antiproliferative activity (maximum reduction 36.8%). No relevant antiproliferative effect of bevacizumab on RGC5 and ARPE19 cells could be observed when used at a concentration of 0.8 mg/ml or lower. CEC and ARPE 19 cells stained positively for VEGF, VEGFR1, and VEGFR2. More than 95% of the CEC were positive for von Willebrand factor. CONCLUSIONS: These experimental findings support the safety of intravitreal bevacizumab when used at the currently applied concentration of about 0.25 mg/ml. Bevacizumab exerts a moderate growth inhibition on CEC when used in concentrations of at least 0.025 mg/ml. However, at higher doses (2.5 mg/ml) bevacizumab may be harmful to the retinal pigment epithelium.

Angiogenesis Inhibitors↗
PubMed2005

Steroidogenic acute regulatory protein in the brain.

The nervous system synthesizes steroids that regulate the development and function of neurons and glia, and have neuroprotective properties. The first step in steroidogenesis involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone by the enzyme cytochrome P450side chain cleavage. The peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein are involved in this process and appear to function in a coordinated manner. Steroidogenic acute regulatory protein mRNA and protein are widely expressed throughout the adult brain. Steroidogenic acute regulatory protein expression has been detected in many neuronal populations, in ependymocytes, in some astroglial cells, in Schwann cells from peripheral nerves and in proliferating cells of the developing and adult brain. Steroidogenic acute regulatory protein is colocalized in the same neural cells with P450side chain cleavage and with other steroidogenic enzymes. Steroidogenic acute regulatory protein expression in the brain shows marked changes with development, aging and injury. The steroidogenic acute regulatory protein gene may be under the control of diverse mechanisms in different neural cell types, since its expression is upregulated by cyclic AMP (cAMP) in gliomas and astrocytes in culture and downregulated by cyclic AMP (cAMP) in Schwann cells. In addition, activation of N-methyl-D-aspartate receptors, and the consequent rise in intracellular calcium levels, activates steroidogenic acute regulatory protein and steroidogenesis in hippocampal neurons. In conclusion, steroidogenic acute regulatory protein is regulated in the nervous system by different physiological and pathological conditions and may play an important role during brain development, aging and after injury.

Animals↗
PubMed2005

Salmonella enterica serotypes isolated from imported frozen chicken meat in the Canary islands.

To determine the prevalence of Salmonella enterica serotypes in imported frozen chicken meat, 406 samples (whole chicken, legs, and breast meat) were analyzed for Salmonella according to ISO6579 rules, serotypes were assigned, and phage typing was conducted for Salmonella serotypes Enteritidis, Typhimurium, and Heidelberg. The overall frequency of Salmonella isolation was 16.5%. By country of origin, the highest percentage of cases was found among the samples from France followed by samples from Brazil. The differences between legs and breast meat were significant. The most frequently isolated serotype of Salmonella was Enteritidis, followed by Salmonella Heidelberg, Salmonella Typhimurium, and Salmonella Virchow. By country of origin, we identified a large percentage of serotype Salmonella Enteritidis in the samples imported from Brazil. There was a greater diversity of serotypes isolated from the French samples, and Salmonella Enteritidis was not the dominant strain. In the samples from the United States, the only serotype isolated was Salmonella Kentucky, although a smaller number of samples was analyzed. The Salmonella Enteritidis phage type that prevailed in both France and Brazil was 4. Phage types 204c and 204 were identified for Salmonella Typhimurium, and phage types 8, 31, and 37 were identified for Salmonella Virchow.

Animals↗
PubMed2004

Brain steroidogenesis: emerging therapeutic strategies to prevent neurodegeneration.

Decreasing levels of gonadal steroids with aging are associated to an increase in cognitive, neurological and psychiatric disturbances. Estradiol is neuroprotective in animal models of neurodegeneration. However, the effects of hormonal replacement therapy on brain function in postmenopausal women are controversial. A possible alternative to hormonal replacement therapy is to increase local brain steroidogenesis, since experimental studies indicate that local estrogen formation in the brain is neuroprotective.

Animals↗
PubMed2004

Comparative evaluation of four commercial tests for presumptive identification of Candida albicans.

Four commercially available tests (Albicans ID2, Chromalbicans Agar, CHROMagar Candida, and BactiCard Candida) and the germ tube (GT) test for presumptive identification of Candida albicans were evaluated using clinical isolates of C. albicans (n=89) and of non-albicans yeasts (n=107). Sensitivities and specificities of all tests regarding the identification of C. albicans were greater than 92%, except for Chromalbicans Agar plates (88.7% after 48 h) and their specificity was 86%. Overall, the four commercial systems were easy to use and are good systems for the routine identification of C. albicans.

Candida albicans↗
PubMed2004

Neurosteroids: the StAR protein in the brain.

The nervous system is a well-known target for steroid hormones, as these hormones regulate brain functions that include neuronal survival and differentiation, myelination, neurogenesis, plasticity and repair after injury. Furthermore, the brain is also a steroidogenic tissue because it possesses the enzymes required to metabolize the common precursor, cholesterol, into steroids, named 'neurosteroids'. The rate-limiting step in the synthesis of steroid hormones is the access of cholesterol, accumulated in the outer mitochondrial membrane, to the first steroidogenic enzyme, P450scc (cholesterol side-chain cleavage enzyme), located in the inner mitochondrial membrane. In the ovary and the adrenal gland, which comprise classic steroidogenic tissues, this process requires the steroidogenic acute regulatory protein (StAR) to facilitate the shuttle of cholesterol through the intermembrane space. The mechanism used by the brain to regulate the first stage of steroidogenesis remains unknown. Recently, several groups have investigated the potential presence of StAR in the nervous tissue and have concluded that StAR is widely expressed throughout the brain, although restricted to specific cell populations. New results concerning localization, regulation and possible functions of StAR in the brain are discussed.

Animals↗
PubMed2002

Comparison of Albicans ID2 agar plate with the germ tube for presumptive identification of Candida albicans.

Albicans ID2 (bioMérieux, France) is a commercially available chromogenic medium that allows rapid and specific macroscopic identification of Candida albicans and facilitates the differentiation of species in mixed cultures. We compared it with the standard method for the identification of yeast species, the germ tube test (GT). This study involved 423 clinical isolates, including 163 C. albicans and 260 non-albicans yeasts. Sensitivity of Albicans ID2 agar plates regarding the identification of C. albicans were 98.2% after 48 h of incubation and specificity of 96.6%. This method using rapid enzymatic method shows the same similar sensitivity than the GT test The false negative rate (1.8%) for the GT test is consistent with that previously reported. None tests discriminated between C. albicans and C. dubliniensis isolates.

Agar↗
PubMed2002

Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis at a university hospital and comparison with antibiotyping and protein A and coagulase gene polymorphisms.

A total of 124 methicillin-resistant Staphylococcus aureus (MRSA) isolates were ascertained at the University Hospital of the Canary Islands between January 1997 and April 2000. Genotyping included pulsed-field gel electrophoresis (PFGE) (SmaI digestion) and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the coagulase (coa) and protein A (spa) genes. Antibiotic resistance was the main phenotypic marker correlated with genotyping results. Three main PFGE types were detected: A (with 12 subtypes), B (with 2 subtypes), and C. PFGE type A1 was the most commonly found (61% of isolates) and the one responsible for all the epidemic outbreaks. Other genetics markers used (coa and spa RFLPs) were significantly correlated with the PFGE types detected (P < 0.001). These PCR-RFLP assays were useful as molecular markers for a quick, preliminary study of MRSA outbreaks.

Anti-Bacterial Agents↗
PubMed2002

Antimicrobial-resistant Salmonella enterica serovars isolated from chickens in Spain.

In order to analyze the antibiotic resistance of Salmonella enterica serovars, a total of 112 Salmonella strains were tested (54 S. enteritidis, 32 S. typhimurium, 11 S. heidelberg, 7 S. infantis, 4 S. virchow and 4 S. hadar). The bacteria were isolated from 691 samples of frozen and fresh chicken meat. Identification of microorganisms and antimicrobial sensitivity testing were undertaken by means of the automated MicroScan AutoScan 4 method (Baxter in Spain). 45.5% of 112 strains tested were susceptible to all antibiotics. The highest percentage of resistance was found to: chloramphenicol (44.6%), ampicillin (34.8%) and tetracycline (33.9%). Multiple resistance was observed in 49 strains (43.7%), whereas single resistance was seen in 12 isolates (10.7%). We found 12 different patterns of resistance in Salmonella enterica serovar enteriditis. Resistance to chloramphenicol was the most common single resistance. The most frequent patterns of multiresistant strains were ampicillin + amoxicillin/clavulanate + cefazolin + imipenem and chloramphenicol + impipenem. In this serotype, 49 isolates belonged to phagetype 4. Salmonella typhimurium showed the highest percentages of resistance to the tested drugs, with six different resistance patterns found. 25 strains out of 32 S. typhimurium isolates belonged to phagotype 120 and 13 of these showed the same resistance pattern: chloramphenicol + tetracycline + ampicillin. The high incidence of antibiotic resistant salmonellae found in chickens in our study suggests the need for public health interventions to decrease selective pressure on bacterial strains by antimicrobial agents.

Animals↗
PubMed2002

Postoperative complications of lung resection after induction chemotherapy using Paclitaxel (and radiotherapy) for advanced non-small lung cancer.

BACKGROUND: Locally advanced non-small-cell lung carcinoma is currently treated by multidisciplinary protocols using a combination of chemotherapy, radiotherapy and surgery. However the best strategy for applying these therapeutic measures has not yet been established. One of the difficulties of using these forms of treatment is their toxicity. Our aim was to determine whether the postoperative course of the disease can be influenced by preoperative chemotherapy in any way. METHODS: Nineteen patients were surgically treated after receiving induction treatment between October 1996 and October 1998. The indications for giving induction treatment were: stage III disease in 12 patients (1 Pancoast tumor), lung cancer and solitary brain metastasis in 4 patients, double primary lung cancer in 3 patients (1 synchronous and 2 metachronous). Variables were the chemotherapy treatment time interval from the beginning to surgery, the type of surgery, postoperative mortality and morbidity. Mean age was 55.9 years old (range between 25 and 70 years). Predominant gender was male (18 men and 1 woman). Neoadjuvant treatment consisted of chemotherapy in all patients (Paclitaxel, Cysplatin and Vinorelbine in cycles for a mean period of 3 months), and radiotherapy (14 patients). Pulmonary resections were: pneumonectomy (2 patients), lobectomy (16 patients) and wedge resection (1 patient). There were no exploratory thoracotomies. Bronchoplasty procedures were necessary in 5 cases and angioplasty in 5. Cardiopulmonary bypass was necessary in 1 case in order to resect an infiltrated pulmonary vein. Intraoperative radiotherapy (IORT) was used in 9 cases. RESULTS: Complications occurred in the immediate postoperative period in 9 patients: 1 postpneumonectomy respiratory distress syndrome, 2 bronchopleural fistulae, 4 prolonged air leaks, 1 complete dehiscence of the thoracotomy scar and 1 colitis caused by anaerobes. The postoperative mortality (within 30 days) was 2 patients (10.5%): 1 died from bronchopleural fistula and the other from postpneumonectomy respiratory distress syndrome. However, if we take into account the fact that the case of anaerobic colitis also ended with the patient's death on the 48th postoperative day, and we include it in the mortality rate, the final mortality is higher (15.8%). CONCLUSIONS: Surgery for non-small-cell lung carcinoma has to be considered a high-risk procedure. But, if patients are selected appropriately and the perioperative management is satisfactory, reasonable rates of morbidity and mortality can be achieved. More studies are needed in order to define the exact role of these therapeutic measures.

Adenocarcinoma↗
PubMed2001

Brain aromatase is neuroprotective.

The expression of aromatase, the enzyme that catalyzes the biosynthesis of estrogens from precursor androgens, is increased in the brain after injury, suggesting that aromatase may be involved in neuroprotection. In the present study, the effect of inactivating aromatase has been assessed in a model of neurodegeneration induced by the systemic administration of neurotoxins. Domoic acid, at a dose that is not neurotoxic in intact male mice, induced significant neuronal loss in the hilus of the hippocampal formation of mice with reduced levels of aromatase substrates as a result of gonadectomy. Furthermore, the aromatase substrate testosterone, as well as its metabolite estradiol, the product of aromatase, were able to protect hilar neurons from domoic acid. In contrast, dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone and a nonaromatizable androgen, was not. These findings suggest that aromatization of testosterone to estradiol may be involved in the neuroprotective action of testosterone in this experimental model. In addition, aromatase knock-out mice showed significant neuronal loss after injection of a low dose of domoic acid, while control littermates did not, indicating that aromatase deficiency increases the vulnerability of hilar neurons to neurotoxic degeneration. The effect of aromatase on neuroprotection was also tested in male rats treated systemically with the specific aromatase inhibitor fadrozole and injected with kainic acid, a well characterized neurotoxin for hilar neurons in the rat. Fadrozole enhanced the neurodegenerative effect of kainic acid in intact male rats and this effect was counterbalanced by the administration of estradiol. Furthermore, the neuroprotective effect of testosterone against kainic acid in castrated male rats was blocked by fadrozole. These findings suggest that neuroprotection by aromatase is due to the formation of estradiol from its precursor testosterone. Finally, a role for local cerebral aromatase in neuroprotection is indicated by the fact that intracerebral administration of fadrozole enhanced kainic acid induced neurodegeneration in the hippocampus of intact male rats. These findings indicate that aromatase deficiency decreases the threshold for neurodegeneration and that local cerebral aromatase is neuroprotective. Brain aromatase may therefore represent a new target for therapeutic approaches to neurodegenerative diseases.

Animals↗
PubMed2001

Characterization of a new brain-derived proteoglycan inhibiting retinal ganglion cell axon outgrowth.

A proteoglycan was identified and isolated from physiological saline extracts of chick embryo brains by using a new monoclonal antibody (hybridoma clone mab Te38). The purified proteoglycan displayed an apparent molecular mass of 2500-3500 kDa, which became reduced to 370 and 600 kDa after digestion with chondroitinase ABC or chondroitinase AC. After additional treatment with keratanase the 600-kDa band was no longer detectable in Western blots. The specific epitope recognized by mab Te38 is an O-linked carbohydrate associated with the core protein. Tenascin-C, an extracellular matrix protein known to associate with several proteoglycans, copurified with the mab Te38 proteoglycan on the immunoaffinity column. Mab Te38 binds to the surface of nonneuronal cells; in sections from the primary visual system, expression is restricted to cells in the optic fissure, the dorsal optic nerve, and the chiasm. No retinal cells were found to express the mab Te38 epitope. The isolated molecule inhibited axon outgrowth from retinal explants when offered bound to a substrate consisting of either matrigel or collagen, chondroitinase treatment did not alter the inhibitory properties. The distribution and in vitro function of the Te38 proteoglycan indicate that it may serve a role in guidance of retinal ganglion cell axons.

Animals↗
PubMed2001

Microsatellite instability is associated with the loss of apoptosis in ductal breast carcinomas.

Metastatic progression in ductal breast carcinomas are related to apoptosis in primary tumors. Frameshift mutations in a single-repeat sequence within the coding region (G)8 of the pro-apoptotic Bax gene have been related to microsatellite instability (MSI) and progression of some carcinomas and lymphomas. The aim of this study was to explore whether the extended lifespan of breast cancer cells can also be triggered by Bax mutation in ductal-breast carcinomas, and whether breast cancer cell MSI is related to the loss of apoptosis. For this purpose we studied frameshift mutations of a microsatellite (G)8 in the third exon of the Bax gene in a series of 105 ductal breast carcinomas, at T1 and T2-3 stages, 45 of which had lymph node metastasis. We analyzed MSI in five sequences of DNA isolated from normal and tumor tissue samples taken from 86 patients, and we explored the relationship between MSI and tumor apoptosis status. Bax mutation was not present in ductal breast carcinomas. MSI (two or more markers altered) was detected in 11.6% of tumors. Loss of apoptosis occurred in 80% (8/10) tumors with MSI, versus 17.8% of tumors without MSI (chi2 test, p = 0.0004), independently of Bax protein expression. We conclude that frameshift mutations of a microsatellite (G)8 of the Bax gene are not critical for the loss of apoptosis in breast cancer, and that loss of apoptosis may be a consequence of overexpression of anti-apoptotic protein Bcl-2 or Bcl-xL. Moreover, MSI in breast carcinomas might be the cause of loss of an apoptotic pathway that is not induced by frameshift mutations of a microsatellite (G)8 of the Bax gene.

Adult↗
PubMed2001

Metastatic behavior of human breast carcinomas overexpressing the Bcl-x(L) gene: a role in dormancy and organospecificity.

The ability of metastatic cells to survive antiapoptotic signals may contribute to the organospecific-spread patterns of clinical metastasis and dormancy. MDA-MB-435 breast cancer cells (435/Bcl-x(L)), which overexpress the Bcl-x(L) gene, were labeled with the luciferase gene and injected orthotopically into homozygous athymic Balb/c (nude) mice to study the metastatic behavior of the breast cancer cells. The overexpression of Bcl-x(L) in tumors increased the overall metastatic burden in mice (bones, liver, kidneys, brain, lungs, and lymph nodes) in comparison with control tumors (435/NEO:luc) during the same time interval (ANOVA, p = 0.005). The principal differences after 110 days were found in bones, which had 1.5 x 10(5) +/- 1.2 x 10(5) tumor cell equivalents (p = 0.03), and lymph nodes, which had 7.0 x 10(6) +/- 6.0 x 10(6) tumor cell equivalents (p = 0.08). The analyses of light production by tissues at different times showed that cells from 435/NEO:luc and 435/Bcl-x(L).luc tumors were detectable in several organs by the second day after intramammary fat pad implantation. Although initially arriving at the target organs in similar numbers, 435/Bcl-x(L) cells developed more metastases than 435/Neo cells, indicating that the Bcl-x(L) gene might have a role in breast cancer dormancy, promoting survival of cells in metastatic foci. Thus, we suggest that overexpression of Bcl-x(L) could counteract the proapoptotic signals in the microenvironment and favor the successful development of metastasis in specific organs.

Analysis of Variance↗
PubMed2001

Spirometry in surgery for anterior mediastinal masses.

STUDY OBJECTIVES: To identify the impact of upright and supine spirometry (USS) on the choice of anesthesia and outcomes in patients undergoing surgery for anterior mediastinal masses (AMMs). DESIGN: Retrospective cohort study. SETTING: A referral, tertiary-care, military medical center. PATIENTS: We reviewed the records of all patients who underwent surgery for AMMs between June 1994 and December 2000 at Walter Reed Army Medical Center. Patients aged > or = 18 years who had "anterior mediastinal mass" listed as the preoperative diagnosis, which had been confirmed by a preoperative CT scan, and who had available preoperative spirometry data were included in our analysis. In cases in which surgery was performed more than once on the same individual, only data from the first operation were evaluated. MEASUREMENTS: Patient demographics, the results of pulmonary function testing, perioperative complications, type of anesthesia, type of surgery, and pathology were used in the evaluation. RESULTS: Thirty-seven patients (median age, 31 years; age range, 19 to 86 years) were included in the final analysis. There were 24 men and 13 women in this group. The mean (+/- SD) seated FVC and FEV(1) values for the group were 4.02 +/- 0.75 L (90.7 +/- 13.3% predicted) and 3.22 +/- 0.56 L 89.6 +/- 14.2% predicted. Twelve patients (32.4%) had USS ordered, and 10 patients (27.0%) had USS performed. USS was ordered significantly more frequently in younger and symptomatic patients (p = 0.022 and p = 0.005, respectively). Spirometry suggestive of possible upper airway obstruction was found in four patients. However, general anesthesia was used in all four patients without complications. Only two patients suffered perioperative complications. One of these patients had normal USS values but underwent surgery under local anesthesia nonetheless. CONCLUSIONS: The recommendation to perform USS prior to surgery on AMMs is based on anecdotal data. Our study found that the incidence of perioperative complications in surgery for AMMs is low. We also found that USS is not ordered in all patients preoperatively and that the results do not always alter the anesthetic technique when abnormal. One patient who experienced a perioperative complication had normal USS values. Larger studies are necessary to further evaluate the utility of USS in surgery for AMMs.

Adult↗
PubMed2001

Successful use of intraoperative radiotherapy for local control of an Askin's tumor recurrence.

Askin s tumor is an infrequent disease, with a high tendency to local recurrence. We present the case of a 16-year-old female diagnosed with a new recurrence of this tumor affecting the thoracic wall. There had been a previous 5-year history of 3 local recurrences treated each time by apparently complete surgery. A multidisciplinary approach consisting of chemotherapy, complete chest tumor resection and intraoperative radiotherapy was undertaken. After 2-year follow-up, the patient is alive and free of disease. The role of surgery is still the key to obtaining good survival, but in this case intraoperative radiotherapy proved to be a good adjuvant treatment.

Adolescent↗