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Biomedical subjects

R Sanchez

Publications and source records attributed to R Sanchez.

At least 19 recordsLinked to original sources

Transfusion-related acute lung injury in the paediatric patient: Two case reports and a review of the literature.

Transfusion-related acute lung injury (TRALI) is increasingly recognized as a major complication of transfusion therapy; it was the leading cause of transfusion-related fatalities in the United States in 2003. Most cases of TRALI that have been reported are in adult patients. We present two cases of TRALI that occurred in children and review the existing literature of paediatric TRALI. The paediatric TRALI case reports highlight two laboratory findings that can help in the diagnosis of TRALI: transient leucopenia and an elevated pulmonary oedema fluid/plasma protein ratio. These two simple diagnostic tests can help rule out other diagnoses and add confidence to the clinical diagnosis of TRALI. Finally, our first case also highlights the potential danger of directed maternal blood donations, which may increase the risk of paediatric TRALI.

Adolescent↗

Gene algebra from a genetic code algebraic structure.

By considering two important factors involved in the codon-anticodon interactions, the hydrogen bond number and the chemical type of bases, a codon array of the genetic code table as an increasing code scale of interaction energies of amino acids in proteins was obtained. Next, in order to consecutively obtain all codons from the codon AAC, a sum operation has been introduced in the set of codons. The group obtained over the set of codons is isomorphic to the group (Z(64), +) of the integer module 64. On the Z(64)-algebra of the set of 64(N) codon sequences of length N, gene mutations are described by means of endomorphisms f:(Z(64))(N)-->(Z(64))(N). Endomorphisms and automorphisms helped us describe the gene mutation pathways. For instance, 77.7% mutations in 749 HIV protease gene sequences correspond to unique diagonal endomorphisms of the wild type strain HXB2. In particular, most of the reported mutations that confer drug resistance to the HIV protease gene correspond to diagonal automorphisms of the wild type. What is more, in the human beta-globin gene a similar situation appears where most of the single codon mutations correspond to automorphisms. Hence, in the analyses of molecular evolution process on the DNA sequence set of length N, the Z(64)-algebra will help us explain the quantitative relationships between genes.

Anticodon↗

Leishmaniasis as an opportunistic infection in HIV-infected patients: determinants of relapse and mortality in a collaborative study of 228 episodes in a Mediterreanean region.

The clinical presentation of visceral leishmaniasis shares similarities with other geographically specific infectious diseases associated with AIDS in terms of relapsing course and atypical presentation. However, visceral leishmaniasis has not, until now, been included in the AIDS case definition. The aim of this study was to describe the clinical features and determinants for relapse and case-fatality of visceral leishmaniasis in HIV-infected patients from a Spanish Mediterranean area. A chart review was conducted in 16 hospitals in the autonomous communities of Valencia and Murcia (Spain). From 1988 to 2001, a total of 228 episodes of visceral leishmaniasis were diagnosed in 155 HIV-infected patients by the detection of amastigotes in bone marrow aspirates or in other tissue samples. Most patients had advanced HIV disease, with a median CD4(+) lymphocyte cell count of 55 cells x 10(9) l, and 56% of them had a previous AIDS-indicator disease. The median duration of follow-up was 8.4 months. HIV-infected patients with visceral leishmaniasis presented with fever (76%), hepatomegaly (77%), splenomegaly (78%), and varying degrees of cytopenias. Leishmania was detected in atypical sites in 22 (14%) patients. A total of 37 (24%) patients had a relapse of visceral leishmaniasis. Female gender was a risk factor for relapse, whereas administration of secondary prophylaxis for visceral leishmaniasis and a completed therapy for visceral leishmaniasis were protective factors against relapse. A total of 86 (54%) patients died. Independent determinants for survival were CD4(+) lymphocyte cell count, completed therapy for leishmania, and secondary prophylaxis for visceral leishmaniasis. The findings show that, in HIV-infected patients, visceral leishmaniasis occurs in late stages of HIV disease and often has a relapsing course. Secondary prophylaxis reduces the risk of relapse. Visceral leishmaniasis in the HIV-infected population should be included in the CDC clinical category C for the definition of AIDS in the same way that other geographically specific opportunistic infections are included.

AIDS-Related Opportunistic Infections↗

Bacteria induce expression of apoptosis in human spermatozoa.

An increased number of sperm undergoing apoptosis has been observed during inflammatory processes in the male genital tract, which might be associated with elevated reactive oxygen species (ROS) levels. However, another factor to stimulate apoptosis could be the direct contact with bacteria or its products, even in the absence of ROS. The aim of this study was to investigate whether bacteria can directly initiate apoptosis in human spermatozoa. Human spermatozoa selected by density gradient centrifugation were incubated with polymorphonuclear granulocytes (PMN) isolated from blood and/or E. faecalis, E. coli or S. aureus. As ROS inductor in PMN, phorbol-12-myristate-13-acetate was used. After incubating the cells for 60 min at 37 degrees C, ROS were determined by chemiluminescence and phosphatidyl serine (PS) externalization was analyzed by flow cytometry with Annexin V-FITC and propidium iodide (PI). The increase in the percentage of spermatozoa Annexin V-FITC-positive/ PI-negative (early event of late apoptosis) was significant after the incubation with PMN plus PMA, PMN plus E. coli and E. coli alone. The percentage of spermatozoa Annexin V-FITC-positive/ PI-positive (apoptosis/necrosis) increased significantly in sperm incubated with E. coli and S. aureus (20.3% +/- 3 and 13.6% +/- 3.2 compared to sperm alone, 6% +/- 0.5). Sperm incubated with PMN-PMA activated showed only a relative increase in apoptosis/necrosis (8.4% +/- 1). Our results show that bacteria directly increase the PS externalisation in ejaculated human sperm. This way of inducing apoptosis does not require external ROS and may result from anyone of the molecular mechanisms that account for changes in motility, vitality and DNA integrity, that are characteristics of spermatozoa in male genital tract infection.

Apoptosis↗

An inverse method for radiation transport.

Adjoint functions have been used with forward functions to compute gradients in implicit (iterative) solution methods for inverse problems in optical tomography, geoscience, thermal science and other fields, but only once has this approach been used for inverse solutions to the Boltzmann transport equation. In this paper, this approach is used to develop an inverse method that requires only angle-independent flux measurements, rather than angle-dependent measurements as was done previously. The method is applied to a simplified form of the transport equation that does not include scattering. The resulting procedure uses measured values of gamma-ray fluxes of discrete, characteristic energies to determine interface locations in a multilayer shield. The method was implemented with a Newton-Raphson optimisation algorithm and it worked very well in numerical 1-D spherical test cases. A more sophisticated optimisation method would better exploit the potential of the inverse method.

Algorithms↗

Nuclear charge radii of 8,9Li determined by laser spectroscopy.

The 2s-->3s transition of (6,7,8,9)Li was studied by high-resolution laser spectroscopy using two-photon Doppler-free excitation and resonance-ionization detection. Hyperfine structure splittings and isotope shifts were determined with precision at the 100 kHz level. Combined with recent theoretical work, the changes in the nuclear-charge radii of (8,9)Li were determined. These are now the lightest short-lived isotopes for which the charge radii have been measured. It is found that the charge radii monotonically decrease with increasing neutron number from 6Li to 9Li.

Journal Article↗

Automated multiresidue analysis of pesticides in olive oil by on-line reversed-phase liquid chromatography-gas chromatography using the through oven transfer adsorption-desorption interface.

A multiresidue, automated and rapid method for the determination of pesticide residues in olive oil is presented. The method employs the through oven transfer adsorption-desorption interface for the on-line coupling of reversed-phase liquid chromatography and gas chromatography. In this fully automated system, olive oil is directly injected with no sample pre-treatment step other than filtration. Methanol-water is used as eluent in the liquid chromatography pre-separation step. The selected liquid chromatography fraction containing the pesticides is automatically transferred to the gas chromatography. The liquid chromatography column flow during elution is different from the flow during the transfer. Using a flame ionisation detector, pesticide detection limits varied from 0.1 to 0.3 mg/l.

Adsorption↗

The effect of small doses of naloxone on the initiation and duration of the first estrus after weaning in sows.

The present research was conducted with the objective of studying the pharmacological effect of small doses of naloxone on the initiation and duration of the first estrus after weaning in the sow. For this purpose, 32 multiparous sows were used. Sows were divided at random into two groups. Group 1 (n=16) was treated by i.m. injection with 2mg naloxone at 12h intervals from 3 days before until 3 days after weaning. Group 2 (n=16) served as the control group and received saline solution at the same times as treatments for group 1. First estrus after weaning occurred at 85+/-5.2 and 108.3+/-5h (P<0.05) in naloxone- and saline-treated sows. Duration of estrus was 89.6+/-3.9 and 49.6+/-3.9h (P<0.05) in naloxone-treated and control animals, respectively. It was concluded that naloxone treatment advanced the time of appearance and duration of the first estrus after weaning in sows giving further support that endogenous opioids (EOP) are modulators of sexual behavior in female pigs.

Animals↗

A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship.

BACKGROUND: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. METHODS: This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/ investigator), symptoms and medication scores as well as the frequency of asthma attacks. RESULTS: In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages. CONCLUSION: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.

Administration, Sublingual↗

First clinical trial of a novel caspase inhibitor: anti-apoptotic caspase inhibitor, IDN-6556, improves liver enzymes.

OBJECTIVE: To evaluate the safety of IDN-6556, a novel anti-apoptotic pan-caspase inhibitor, administered in single and multiple ascending doses in normal volunteers and patients with hepatic dysfunction. MATERIALS AND METHODS: IDN-6556 was administered as a 30-minute intravenous infusion in rising doses to 3 groups: Group A, normal volunteers, given as a single infusion, Group B, normal volunteers, given q.i.d. for 7 days, Group C, patients with hepatic impairment (elevated transaminases, alanine transaminase, ALT and aspartate transaminase, AST), given q.i.d. for 7 days. RESULTS: The drug was well tolerated up to 10 mg/kg/infusion for a single dose, and 1.5 mg/kg/infusion q.i.d. for 7 days, with the dose-limiting adverse event of phlebitis or inflammation at the site of the infusion. This toxicity was predicted from animal studies. Clinically and statistically meaningful dose-related falls in transaminases were seen in all but 1 of the hepatic impaired patients. Two-way ANOVA analyses of the changes for all the IDN-6556 groups combined versus placebo were: ALT absolute change: p < 0.0001 and % change: p = 0.012, AST absolute and % changes: p < 0.0001. After discontinuation of the drug (after 7 days of dosing), the transaminases rapidly returned to the pre-treatment levels. CONCLUSIONS: Following intravenous administration of a novel anti-apoptotic caspase inhibitor, adverse events were mild-to-moderate in severity, resolved in a few days and did not result in any subject terminating treatment prematurely. The effects in hepatic impaired patients appear to be consistent with both the administration and subsequent abrupt withdrawal of an effective hepatoprotective drug that delays cell death in hepatocytes.

Adult↗

High-beta equilibria of drift-optimized compact stellarators.

Compact stellarator configurations have been obtained with good neoclassical confinement that are stable to both pressure- and current-driven modes for high values of beta. These configurations are drift-optimized tokamak-stellarator hybrids with a high-shear tokamak-like rotational transform profile and /B/ that is approximately poloidally symmetric. The bootstrap current is consistent with the required equilibrium current and, while larger than that in existing stellarators, is typically only a small fraction (1/3-1/5) of that in an equivalent tokamak. These configurations have strong magnetic wells and consequently high interchange stability beta limits up to beta=23%. Because of the reduced bootstrap current, these configurations are stable to low-n ideal MHD kink modes with no wall stabilization for values of beta ( approximately 7%-11%) significantly larger than in an equivalent advanced tokamak.

Journal Article↗

Avalanche structure in a running sandpile model.

The probability distribution function of the avalanche size in the sandpile model does not verify strict self-similarity under changes of the sandpile size. Here we show the existence of avalanches with different space-time structure, and each type of avalanche has a different scaling with the sandpile size. This is the main cause of the lack of self-similarity of the probability distribution function of the avalanche sizes, although the boundary effects can also play a role.

Journal Article↗

Application of a factorial design to the study of the flow behavior, spreadability and transparency of a Carbopol ETD 2020 gel. Part II.

A factorial design (2(3)) is applied to study the influence of three of the components of a cosmetic gel (the concentrations of Carbopol ETD 2020, ethanol and glycerine) on flow parameters (Casson's yield value (tau(c)), Casson's viscosity (eta(c)) and apparent viscosity at 125 s-1 (eta(ap.) 125 s-1), spreadability, and transparency. The first-order polynomial equation allowed by the model suitably accounts for the tau(c) and spreadability. Both depend on the concentrations of Carbopol and ethanol, and tau(c) also depends on the ethanol-glycerine interaction. The model explains to a certain extent the complex relationships that are established between the components and that influence eta(c) y eta(ap.) 125 s-1. Transparency is independent of the Carbopol concentration and it is also thought to be independent of the ethanol concentration. In addition, a high linear correlation has been found between the tau(c) and spreadability and other viscoelastic parameters of the gels that were previously determined (Int. J. Pharm. (2001)). The application of the technique of experimental design has been shown to be a very useful tool for formulating gels.

Acrylic Resins↗

[Initial shock from burns. Physiopathology: therapeutic principles].

Widespread destruction of the skin induces a large necrotic mass and a break of the skin barrier. It also leads to an intense inflammatory reaction. This activates keratinocytes, endothelial cells and neutrophils. Certain mediators (e.g. endothelin, histamine, bradykinin, serotonin, catecholamines, vasopressin, prostaglandins, cytokines and nitrogen monoxide) are thus released in large quantities and act both at the site of the burns and at a distance. The abnormally high level of albumin in the capillary wall and the increased capacity of absorption of the interstitial areas around the burns are the main abnormalities observed. This results in a hypovolemia associated with a hemoconcentration, hyponatremia, hypoalbuminemia, systemic vasoconstriction and myocardial malfunction, which is difficult to evidence. During the initial phase, the major risk is the appearance of hypovolemic shock, which is rapidly irreversible if early treatment is not administered. Vascular filling with iso- or hyper-osmolar sodium crystalloids, associated with buffer solutions, is the first line. There is still debate regarding the best moment at which to give albumin. A hyperkinetic shock may occur after several hours and despite the filling. The symptoms are tachycardia, increased heart rate and a dramatic decrease in systemic vascular resistance. This may lead to metabolic acidosis and multi-organ failure. Study of the hemodynamic profile of the patient allows the rational use of pressor amines and haemodialysis.

Blood Coagulation↗

Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer.

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.

Animals↗

Non-immunogenic murine hepatocellular carcinoma Hepa1-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+ T-cell immunity against the parental tumor.

Hepatocellular carcinoma is a lethal disease and methods that develop effective cellular-based immunotherapy are needed. We retrovirally transduced non-immunogenic mouse Hepa1-6 hepatoma cells with the gene encoding the membrane form of macrophage colony stimulating factor (mM-CSF). Excess recombinant M-CSF and phagocytosis-inhibiting chemicals blocked macrophage-mediated killing of cloned mM-CSF transfected Hepa1-6 hepatoma cells. Macrophages derived from Hck(-/-)Fgr(-/-) and Lyn(-/-) triple knockout mice, which are incapable of performing phagocytosis, failed to kill the mM-CSF transduced cells. The mM-CSF transfected tumor clones failed to grow when injected into C57BL/6 or C57L/J mice. Splenocytes from these vaccinated mice displayed cytotoxicity against parental Hepa1-6 cells, but not against B16 and CT-26 tumor cells in vitro. Mice that rejected the mM-CSF transfected Hepa1-6 tumor subsequently rejected parental Hepa1-6 cells but not the B16 melanoma cells when rechallenged. Elimination of the CD8+ effector cells by an anti-CD8 antibody and complement treatment prevented the adoptive transfer of anti-Hepa1-6-specific immunity into naive animals. Thus, mM-CSF provides a method of generating effective anti-tumor immune responses by macrophages and cytotoxic T cells against the parental Hepa1-6 cells. Our work suggests that mM-CSF transduced hepatoma cells could be used as a tumor vaccine to stimulate immune responses against hepatocellular carcinoma.

Animals↗

Fast track as a routine for open heart surgery.

OBJECTIVE: Evaluation of thoracic epidural analgesia (TEA), normothermic cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine procedure for fast track open heart surgery. METHODS: Consecutive patients (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the combination of general anaesthesia using ultra-short acting opiates, TEA, normothermic CBP, normothermic whole blood cardioplegia. Operative procedures included coronary artery bypass grafting (CABG), valve replacement, combined CABG and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent were in Tuman score 0--5 and 20% in score >5. RESULTS: All patients were extubated within 10 min after skin closure. There was one myocardial infarction. Four percent were shortly treated with cathecholamines. Postoperative atrial fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were encountered. No neurological disturbance related to the use of TEA was seen. Seven patients were reoperated because of bleeding. Blood transfusion was given to 6.4% of the patients. Mortality was 0.8%. CONCLUSIONS: The combined methods provides a way for routine immediate postoperative extubation, with low morbidity and short hospital stay.

Adult↗