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Biomedical subjects

E Medina

Publications and source records attributed to E Medina.

At least 19 recordsLinked to original sources

[Complications of endoscopic retrograde cholangiopancreatography in patients aged more than 90 years old].

INTRODUCTION: To evaluate the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and the complication rates of this procedure in patients aged 90 years and older. PATIENTS AND METHOD: A descriptive, prospective study including 42 endoscopic procedures performed from first January 2001 until first June 2004 in 36 patients (7 males and 29 females) was performed. The mean age was 91 years (range 90-96 years). All patients underwent the following: a) clinical evaluation before and after endoscopic exploration; b) evaluation of the success or failure of the endoscopic procedure and c) assessment of complications (perforation, hemorrhage, pancreatitis and infection). Concurrent associated illnesses, as well as the existence of anatomical alterations in Vaters papilla (duodenal diverticula), were also evaluated. RESULTS: ERCP was successful in 85.7% of all explorations performed. Twenty-three patients (63.8%) had one or more major associated diseases. In 15 patients (33.3%) Vaters papilla was associated with duodenal diverticula. The complication rates were as follows: 1) acute pancreatitis in 2 explorations (4.7%), one mild (2.35%) and the other moderate (2.35%); 2) hemorrhage after endoscopic sphincterotomy in 2.8% of patients (1/35); 3) bacteriemia in one patient (2.3%) and cholangitis in one patient (2.3%), with no cases of secondary cholecystitis; 4) hypoxemia in one patient. There were no perforations or deaths related to the procedure. CONCLUSION: ERCP is a safe and effective technique with a low complication rate in patients aged 90 years or older.

Age Factors↗

Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model.

Fibronectin binding protein F1 (Sfb1) of Streptococcus pyogenes (group A streptococcus [GAS]) is a well-characterized adhesin that has been shown to induce protection in mice against a lethal intranasal GAS challenge after intranasal immunization with cholera toxin B subunit (CTB) as adjuvant. With a murine skin infection model, we have shown that Sfb1/CTB vaccination neither elicits opsonizing antibodies nor prevents systemic bacterial growth and dissemination to internal organs after a subcutaneous GAS challenge. These results indicate that an Sfb1-based vaccine should be complemented with additional protective antigens in order to be used in areas such as the tropical north of Australia, where the skin is the primary route of entry for invasive streptococcal diseases.

Adhesins, Bacterial↗

Ionic shell and subshell structures in aluminum and gold nanocontacts.

Conductance histograms of aluminum and gold nanocontact rupture are studied experimentally and simulated using embedded atom potentials to assess the interplay between electronic and structural properties at room temperature. Our results reveal a crossover from quantized conductance structures to crystalline faceting or geometric shell/subshell structures at 300 K. The absence of electronic shell structure in gold and aluminum is in stark contrast with the behavior of alkaline metal nanowires which emulate their cluster counterparts. Semiclassical arguments suggest why rapid dominance of ionic structures takes place, and possible nanowire architectures are proposed in consistency with both the experimental and simulated nanocontact data.

Journal Article↗

Prospective evaluation of magnetic resonance cholangiopancreatography in patients with biliary disease: comparative study with conventional ultrasonography and endoscopic retrograde cholangiopancreatography diagnostic algorithm.

BACKGROUND: Magnetic resonance cholangiopancreatography is an accurate technique that can replace invasive diagnostic methods of the biliary and pancreatic duct. AIMS: Our aim was to assess sensitivity and specificity of magnetic resonance cholangiopancreatography and ultrasonography using the results of endoscopic retrograde cholangiopancreatography as reference, and to establish a diagnostic algorithm under which circumstances magnetic resonance cholangiopancreatography can replace endoscopic retrograde cholangiopancreatography. PATIENTS: Eighty-three patients with suspicion of biliary disease based on clinical, biochemical and ultrasonography findings were studied. METHODS: Ultrasonography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were performed, comparing the results of the techniques for the determination of their sensitivity and specificity. RESULTS: Sensitivity and specificity results obtained by magnetic resonance cholangiopancreatography were: 100 and 92.8% when dilated ducts were detected (n=61); 97.4 and 97.2% in the diagnosis of choledocholithiasis (n=38); 100 and 96.7% in malignant lesions (n=14) and 81.8 and 98.4% when biliary ducts were normal. The percentage of images of diagnostic quality was 97.6%. Sensitivity and specificity achieved by ultrasonography was: 100 and 57.1% in detection of dilatation, 71 and 97.2% in choledocholithiasis, 92.8 and 96.7% in malignancy and 66.6 and 96.8% in normal ducts. CONCLUSIONS: Magnetic resonance cholangiopancreatography is a technique with high sensitivity and specificity in the evaluation of biliary ducts. Thus, magnetic resonance cholangiopancreatography may replace diagnostic endoscopic retrograde cholangiopancreatography for purely diagnostic purposes, following an initial clinical and ultrasonographic exam.

Adult↗

Viscosity minimum in bimodal concentrated suspensions under shear.

We study a model of concentrated suspensions under shear in two dimensions. Interactions between suspended particles are dominated by direct-contact viscoelastic forces and the particles are neutrally bouyant. The bimodal suspensions consist of a variable proportion between large and small droplets, with a fixed global suspended fraction. Going beyond the assumptions of the classical theory of Farris (R.J. Farris, Trans. Soc. Rheol. 12, 281 (1968)), we discuss a shear viscosity minimum, as a function of the small-to-large-particle ratio, in shear geometries imposed by external body forces and boundaries. Within a linear-response scheme, we find the dependence of the viscosity minimum on the imposed shear and the microscopic drop friction parameters. We also discuss the viscosity minimum under dynamically imposed shear applied by boundaries. We find a reduction of macroscopic viscosity with the increase of the microscopic friction parameters that is understood using a simple two-drop model. Our simulation results are qualitatively consistent with recent experiments in concentrated bimodal emulsions with a highly viscous or rigid suspended component.

Journal Article↗

Genetic control of susceptibility to group A streptococcal infection in mice.

The influence of genetic background on the ability to control infection with group A streptococci was investigated in different inbred strains of mice. Whereas BALB/c, C57BL/10, and DBA/2 mice were the most resistant strains, with lower bacteria loads and higher survival times, C3H/HeN and CBA/J mice exhibited substantially higher bacterial growth and 100% mortality. Differences in susceptibility were not dependent on the inoculum size. Resistance was influenced by sex, with males being much more susceptible than females. B cell- and T cell-deficient mice from the resistant background were as resistant to infection as were immunocompetent mice, which suggests that the effector mechanisms are independent of adaptive immunity. These results demonstrate for the first time the influence of genetic background and sex on susceptibility to infection with Streptococcus pyogenes in mice. The use of this mouse model of group A streptococcal infection will allow for a better definition of parameters involved in the outcome of the disease.

Animals↗

Role played by the response regulator Ris in Bordetella bronchiseptica resistance to macrophage killing.

Previous studies suggested that the persistence in eukaryotic cells of a Bordetella bronchiseptica mutant carrying an insertion in the locus encoding the response regulator RisAS is impaired. This suggested that ris-dependent products are required for the intracellular survival of bacteria. In this study we demonstrate that ris-regulated products play a role in B. bronchiseptica resistance against both phagosomal acidification and reactive oxygen intermediates.

Adenosine Triphosphatases↗

From favorable atomic configurations to supershell structures: a new interpretation of conductance histograms.

Simulated minimum cross-section histograms of breaking Al nanocontacts are produced using molecular dynamics. The results allow a new interpretation of the controverted conductance histogram peaks based on preferential geometrical arrangements of nanocontact necks. As temperature increases, lower conductance peaks decrease in favor of broader and higher conductance structures. This reveals the existence of shell and supershell structures favored by the increased mobility of Al atoms.

Journal Article↗

Use of live bacterial vaccine vectors for antigen delivery: potential and limitations.

Most infectious agents are restricted to the mucosal membranes or their transit through the mucosa constitutes a critical step in the infection process. Therefore, the elicitation of an efficient immune response, not only at systemic, but also at mucosal level, after vaccination is highly desirable, representing a significant advantage in order to prevent infection. This goal can be only achieved, when the vaccine formulation is administered by the mucosal route. However, soluble antigens given by this route are usually poorly immunogenic. Among the available approaches to stimulate efficient mucosal responses, the use of bacterial carriers to deliver vaccine antigens, probably, constitutes one of the most successful strategies. The potential and limitations of the most extensively studied bacterial carrier systems will be discussed.

Bacillus anthracis↗

[Colonoscopic follow-up of patients undergoing curative resection of colorectal cancer].

AIM: To investigate the role of colonoscopy in the follow-up of patients undergoing curative resection of colorectal cancer. MATERIAL AND METHODS: A prospective study was performed of 102 patients with colorectal cancer who underwent surgery with curative intention. Postoperative colonoscopic follow-up was a minimum of 5 years. RESULTS: There were 62 males and 40 females. The mean duration of follow-up was 73.4 months. Synchronous polyps were found in 44.1% (114 in 45 patients) and metachronous polyps in 33.4% (64 in 34 patients). Synchronous carcinoma was detected in 7.8% (9 in 8 patients), metachronous carcinoma in 1.9% (2 in 2 patients) and suture recurrence in 4.9% (5 in 5 patients). Metachronous polyps developed in 55.5% of the patients with synchronous polyps and in only 15.8% of those with no synchronous polyps (p < 0.00005); the odds ratio was 6.67. Colonoscopy diagnosed 92 synchronous polyps and 64 metachronous polyps; of these, 34 were found to be significant(in 22 patients). Colonoscopy diagnosed 5 synchronous carcinomas; in 3 of these (polyps with non-invasive carcinoma) polypectomy constituted definitive therapy and in the remaining 2, curative resection was achieved. Colonoscopy diagnosed 2 stage C2 metachronous carcinomas at 63 and 94 months. Curative resection was achieved in both cases. Colonoscopic follow-up diagnosed 2 suture recurrences and resection was potentially curative. CONCLUSIONS: Colonoscopy was found to play an essential role in 30% of the patients. The technique allowed the early diagnosis of synchronous carcinomas and curative treatment of metachronous carcinomas and demonstrated that the presence of synchronous polyps increases the risk of developing metachronous polyps.

Adenomatous Polyps↗

The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen.

Human keratinocyte motility plays an important role in the re-epithelialization of human skin wounds. The wound bed over which human keratinocytes migrate is rich in extracellular matrices, such as fibrin, fibronectin, and collagen, and serum factors, such as platelet-derived growth factor and transforming growth factor beta 1. Extracellular matrices and the serum factors bind to cell surface receptors and initiate a cascade of intracellular signaling events that regulate cell migration. In this study, we identified an intracellular signaling pathway that mediates collagen- driven motility of human keratinocytes. Pharmaco logic inhibition of the activation of p38-alpha and p38-beta mitogen-activated protein kinase activation potently blocked collagen-driven human keratinocyte migration. Transfection of the same keratinocytes with the kinase-negative mutants of p38-alpha or p38-beta mitogen-activated protein kinase markedly inhibited keratinocyte migration on collagen. Attachment of keratinocytes to collagen activated p38 mitogen- activated protein kinase, as well as p44/p42 ERKs. Interestingly, activation of the p38 mitogen-activated protein kinase cascade by overexpressing the constitutively active MKK3 and MKK6, MKK3b(E) and MKK6b(E), could neither initiate migration in the absence of collagen nor enhance collagen-driven migration. This study provides evidence that the p38-MAPK/SAPK pathway is necessary, but insufficient, for mediating human keratinocyte migration on collagen.

Calcium-Calmodulin-Dependent Protein Kinases↗

Characterization of the domain of fibronectin-binding protein I of Streptococcus pyogenes responsible for elicitation of a protective immune response.

Fibronectin-binding protein I (SfbI) represents a major adhesin of Streptococcus pyogenes. Mice were intranasally immunized with recombinant proteins spanning different portions of SfbI to identify the minimal fragment able to elicit a protective response against a lethal challenge with S. pyogenes. The strongest cellular responses and the highest levels of antigen-specific secretory immunoglobulin A (IgA) were detected in mice immunized with the fibronectin-binding region of SfbI. In contrast, animals vaccinated with a polypeptide spanning the aromatic and proline-rich regions showed the highest titers and fastest IgG response in serum. Vaccination with either SfbI without a membrane anchor and signal peptide or a polypeptide encompassing its fibronectin-binding regions resulted in efficient protection against heterologous challenge (60% and 80%, respectively), whereas the use of a polypeptide lacking this region conferred marginal protection (10%) with respect to the control group (0%). These results demonstrate that the fibronectin-binding region of SfbI is a promising candidate antigen for developing anti-S. pyogenes vaccines.

Adhesins, Bacterial↗

Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy.

OBJECTIVE: To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN: Retrospective modelling study. PATIENTS AND PARTICIPANTS: 18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9.1 years) who required conversion to tacrolimus because of acute or chronic rejection or cyclosporin toxicity. METHODS: 287 whole-blood tacrolimus concentrations from therapeutic drug monitoring were used to build a nonlinear mixed-effects population model (NONMEM program) for the apparent clearance of tacrolimus. Variables considered were age, total bodyweight (TBW), body surface area (BSA), time after initiation of treatment (T), gender, haematocrit (Hct), albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gammaGT), alkaline phosphatase (ALP), bilirubin (BIL), creatinine clearance (CL(CR)) and dosage of concomitant corticosteroids (EST). RESULTS: TBW, T, BIL and ALT were the covariates that displayed a significant influence on CL according to the final regression model: CL (L/h) = 10.4(TBW/70)3/4 x e(-0.00032 T) x e(-0.057 BIL) x (1 - 0.079 ALT). With this model, the estimates of the coefficients of variation were 24.3% and 29.5% for interpatient variability in CL and residual variability, respectively. CONCLUSIONS: The proposed model for tacrolimus CL can be applied for a priori dosage calculations, although the results should be used with caution because of the unexplained variability in the CL. We therefore recommended close monitoring of tacrolimus whole blood concentrations, especially within the first months of treatment. The best use of the model would be its application in dosage adjustment based on therapeutic drug monitoring and the Bayesian approach.

Adolescent↗

[Diet, smoking and reproductive history as risk factor for cervical cancer].

BACKGROUND: Epidemiological studies have suggested that smoking, nutrition and sexual patterns are major risk factors for cervical cancer. AIM: To study the association between food consumption patterns, smoking and sexual behavior and the risk of cervical cancer. MATERIAL AND METHODS: A matched case control study of 170 cases and 340 controls. Food and nutrient intakes were assessed by a food frequency questionnaire considering 58 antioxidant rich food items. Median daily intake of vegetables, fruits, antioxidant vitamins and fiber was calculated. A conditional logistic regression model was used to determine odds ratios associated with variations in nutritional intake and no nutritional factors (age at first delivery, parity, body mass index, family history of cancer and smoking). RESULTS: High intakes of vegetables, fruits, beta carotene, vitamin C, E and fiber were associated with a lower risk of cervical cancer (Odds ratios ranging from 0.56 to 0.78). The risk for cancer was inversely associated with the age at first delivery and directly associated with the total number of pregnancies and smoking. Multivariate analysis model showed a protective effect for vegetable and vitamin E consumption (odds ratio of 0.6 with confidence intervals of 0.5 to 0.8 p < 0.001) and a higher risk associated to smoking (odds ratio 2.8, confidence intervals 1.5-5.5 p < 0.002) and a younger age at the first delivery (odds ratio 3.37 confidence intervals 2-5.3 p < 0.001). CONCLUSIONS: Cervical cancer is associated with reproductive and food consumption behaviors. A higher intake of vegetables and foods rich in vitamin E can reduce its risk.

Adult↗

[Cancer mortality in Chile: epidemiological considerations].

Malignancies are the second most important cause of mortality in Chile, accounting for 21.8% of total deaths. In comparison with other causes, cancer mortality shows an upward trend with increasing mortality rates from 99 to 118 per 100.000 population in the period 1980-1998. The most important cancer locations are stomach, lung and prostate among men and gallbladder, stomach, breast and uterine cervix in women. According to present risks, the mean probability for a Chilean to die from cancer is 3.0% for stomach, 2.3% for prostate, 2.0% for lung, 1.7% for gallbladder, 1.6% for breast and 1.2% for uterine cervix cancer. Recent trends of cancer crude death rates are a matter of concern. During the period 1990-1998 a significant decrease of death rates was only noticed for uterine cervix cancers. On the other hand, important increases were observed for prostate, lung, gallbladder, colon and kidney cancers. If death rates are adjusted by age, an increased risk, not due to the population aging process, is noticed for prostate and to less extent for kidney, colon, skin and myeloma. The adjusted rates show a downward trend for uterine cervix, stomach, breast and esophagus cancer. Increasing cancer mortality is associated with diagnostic and therapeutic delays. Possible actions in screening programs are discussed.

Adolescent↗

Development and characterization of a recombinant truncated type VII collagen "minigene". Implication for gene therapy of dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is an inherited mechano-bullous disorder of skin caused by mutations in the type VII collagen gene. The lack of therapy for DEB provides an impetus to develop gene therapy strategies. However, the full-length 9-kilobase type VII collagen cDNA exceeds the cloning capacity of current viral delivery vectors. In this study, we produced a recombinant type VII minicollagen containing the intact noncollagenous domains, NC1 and NC2, and part of the central collagenous domain using stably transfected human 293 cell clones and purified large quantities of the recombinant minicollagen VII from culture media. Minicollagen VII was secreted as correctly-folded, disulfide-bonded, helical trimers resistant to protease degradation. Purified minicollagen VII bound to fibronectin, laminin-5, type I collagen, and type IV collagen. Furthermore, retroviral-mediated transduction of the minigene construct into DEB keratinocytes (in which type VII collagen was absent) resulted in persistent synthesis and secretion of a 230-kDa recombinant minicollagen VII. In comparison with parent DEB keratinocytes, the gene-corrected DEB keratinocytes demonstrated enhanced cell-substratum adhesion, increased proliferative potential, and reduced cell motility, features that reversed the DEB phenotype toward normal. We conclude that the use of the minicollagen VII may provide a strategy to correct the cellular manifestations of gene defects in DEB.

Cell Line↗

Subchronic administration of sublethal doses of thallium to rats: effects on distribution and lipid peroxidation in brain regions.

Occupational exposure to thallium (Tl+) is known to be responsible for severe neurological manifestations in humans, including ataxia and paralysis; however, little is known yet about the precise mechanism of toxicity elicited by this heavy metal at sublethal doses and its brain distribution after chronic or subchronic exposures resulting from environmental contamination. In order to evaluate the levels of Tl in rat brain regions after a subchronic administration (30 days) of sublethal doses of Tl (I) acetate: 0.8 mg/kg (1/40 of LD(50)), 1.6 mg/kg (1/20 of LD(50)), we measured the concentrations of Tl by atomic absorption spectrophotometry. A possible role of oxidative injury in the pattern of toxicity exerted by Tl in the same brain regions, was also studied. Lipid peroxidation (LP) as a current marker of oxidative stress, was estimated by the generation of lipid fluorescent products. Higher concentrations of Tl were observed in brain tissue from adult rats treated with 1.6 mg/kg, as compared to those treated with 0.8 mg/kg. However, no differential distribution of Tl among regions was observed after administration of 0.8 mg/kg dose to rats, nor after 1. 6 mg/kg dose. We also found significant changes in LP both in corpus striatum and cerebellum from rats treated daily with 0.8 mg/kg Tl, whereas all regions from rats treated with 1.6 mg/kg Tl exhibited enhanced LP as compared to control. These findings suggest an active role of free radicals and oxidative events involved in the pattern of toxicity after exposure to sublethal doses of Tl, which are associated with regional susceptibility of the brain to this metal.

Animals↗