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Biomedical subjects

R M Torres

Publications and source records attributed to R M Torres.

At least 19 recordsLinked to original sources

LC-ESI-MSD fast determination of residual mitomycin C in hen aqueous humour after corneal refractive surgery.

A simple, fast and reliable method has been developed for the assay of traces of mitomycin C (MMC) in hen aqueous humour samples. The determination was carried out by high-performance liquid chromatography with electrospray ionization mass spectrometric detection. In isocratic elution analysis, the mobile phase was a mixture of water-acetonitrile (78:22, v/v) and the chromatographic column was C(18) at 35 degrees C. The method has been validated over a range from 0.1 to 250 microg L(-1) in hen aqueous humour with correlation coefficients higher than 0.999. Limit of detection and limit of quantification for MMC based in signal to noise ratio of 3 and 10, respectively, were 20 and 71 ng L(-1). The developed method allows the analysis of MMC in hen aqueous humour samples obtained at different times and conditions in order to evaluate and compare the efficacy of the drug administration.

Acetonitriles↗

[Corneal biomechanics].

OBJECTIVE: To review the corneal biomechanic concepts and to analyse, clarify and understand their relevance in refractive surgery. MATERIALS AND METHODS: A literature review has been done using different databases. RESULTS: Corneal biomechanic concepts are not new and are applied implicitly in numerous surgical procedures. Their origin is related to tonometry studies, but they gained in popularity when they were linked to the treatment of keratoconus, a pathology in which the mechanical properties of the cornea are altered. Factors determining corneal stability were thus defined. Corneal biomechanics have also been used following refractive surgery to study post-operative keratectasia and to improve ablation patterns, which ignores the corneal response. The new ablation systems need to include the biomechanical factors, which motivate research conducted in physical-mathematical models and in corneal wound healing, improving our knowledge about the corneal biomechanical response. CONCLUSIONS: The corneal biomechanic concepts have gained in popularity with the advent of refractive surgery, although they did exist previously. Their relevance is linked to improvements in the ablation systems used in an attempt to obtain more accurate and reliable results.

Biomechanical Phenomena↗

Previous cognitive impairment and failure to thrive syndrome in patients who died in a geriatric convalescence hospitalization unit.

Cognitive impairment and depression are commonly associated with poor outcomes in geriatric patients. Both are part of the "failure to thrive syndrome" (FTS), that is a combined group of symptoms as a result from progressive functional, mental and nutritional impairment status in older patients. This paper was aimed at evaluating the presence of FTS in the patients who died in a geriatric convalescence unit (GCU) (intermediate care facility) and comparing the characteristics of patients with primary FTS (not associated with an evident identifiable disease) and secondary FTS (associated with an evident identifiable disease). Finally, we wanted to analyze if the presence of cognitive impairment before admission was associated with the type of FTS. We analyzed 78 patients retrospectively. The presence of the next three conditions was necessary to define the FTS: (i) Impaired functional status and malnutrition. (ii) Cognitive impairment and/or depression. (iii) Absence of improvement, after a specific geriatric intervention program during the hospitalization. Functional status for basic and instrumental activities of daily living (ADL and IADL) and the presence of symptoms cognitive impairment before admission were evaluated. Of the 78 analyzed patients, there were 30 (38.4%) with symptoms of FTS. Seventeen of them (56.6%) had a secondary FTS and 13 (43.3%) a primary one. This last group of patients had a significantly higher mean age (84.7 +/- 5.8 vs. 78.6 +/- 7.2; p < 0.02) and before admission they were significantly more dependent for ADL: 10 patients (76.9%) vs. 7 (41.0%) chi2 = 3.833, p < 0.05. A higher proportion of subjects with cognitive impairment before admission was found in the group of patients with primary FTS, than in those secondary FTS, although this difference did not reach statistical significance. Patients with primary FTS seem to be older and more dependent for ADL before admission, than those with secondary FTS.

Aged↗

Clinical impact of different scores of the mini nutritional assessment (MNA) in the diagnosis of malnutrition in patients with cognitive impairment.

It was aimed at evaluating the clinical usefulness of the mini nutritional assessment (MNA) to identify malnutrition in elderly patients with cognitive impairment, admitted to a geriatric convalescence unit (intermediate care facility). Sixty-three patients with cognitive impairment were studied. Cognitive impairment was considered when mini mental state examination (MMSE) scores were below 21. MNA and a nutritional evaluation according to the sequential model of the American Institute of Nutrition (AIN) were performed at admission. According to the AIN criteria, malnutrition was considered, if there were abnormalities in at least one of the following parameters: albumin, cholesterol, body mass index (BMI), and branchial circumference. Based on these criteria, 27 patients (42.8%) proved to be undernourished at admission, whereas if taking the original MNA scores, 39 patients (61.9%) were undernourished, 23 (36.5%) were at risk of malnutrition, and 1 (1.5%) was normal. The analyzed population was divided in four categories (quartiles) of the MNA scores: very low (</= 13.5), low (> 13.5 and </= 16), intermediate (> 16 and </= 18.5) and high (> 18.5). Likelihood ratios of each MNA quartile were obtained by dividing the percentage of patients in a given MNA category who were undernourished (according to AIN) by the percentage of patients in the same MNA category who were not undernourished. In the very low MNA quartile, this likelihood ratio was 2.79 and for the low MNA quartile it was 0.49. For intermediate and high MNA categories, likelihood ratios were 1.0 and 0.07 respectively. In the present study, MNA identified undernourished patients with a high clinical diagnostic impact value only, when very low scores (</= 13) are obtained.

Aged↗

Validation of a modified version of the Gijon's social-familial evaluation scale (SFES): the "Barcelona SFES Version", for patients with cognitive impairment.

The aim was to validate an abbreviated version of the Gijon's social-familial evaluation scale (SFES) (Barcelona-SFES version), on patients with cognitive impairment. A group of 34 patients with cognitive impairment, admitted to an intermediate-long-term-care facility, were analyzed. Mean age was 80.2 +/- 7.4 years. Gijón's SFES was abbreviated and only the first three item groups corresponding to family conditions, social contacts and assistance from the social network were selected. Barcelona-SFES version had a range score between 3 to 15 points, in which low scores identify older patients who live with their family, have good contacts, and participate in community activities. In contrast, high scores identify older persons who live alone and have poor social support and little participation with community activities. Three social risk categories were established according to the Barcelona-SFES score: low social risk (>/= 7 points), intermediate social risk (8-9 points) and high social points). Validation criteria used in the present study were: predictive value of Barcelona-SFES score of post-discharge destination (home or institution), and patient's (or family's) request for a definitive institutionalization in a nursing home. There were 9 patients with low social risk (26.4 %), 8 with intermediate social risk (23.5 %) and 17 with high social risk (50 %). A significant relationship between Barcelona-SFES scores and post-discharge destination was found. Eighty percent of patients discharged to an institution(nursing and residential homes), they had high social risk SFES scores (>/= 10) Also, a significant correlation was found between the number of patients for which a definitive institutionalization request was performed and the Barcelona-SFES scores. Fifteen (88.2 %) of the 18 patients for whom the request was done, were in the high social risk group. The lowest scores from SFES were predictive of home discharge, while the highest scores were predictive of a definitive institutionalization.

Aged↗

Observational scale and geriatric depression scale of Yesavage to identify depressive symptoms in older patients.

The diagnosis of depression by clinical interview may be difficult in the patients with communication problems (aphasia, severe cognitive impairment or severe deafness). In these cases, depressive symptoms may be observed by others (nurses and caregivers). The aim of this study was to evaluate the clinical usefulness of an observational scale to identify depression in older patients. Seventy-six institutionalized patients in an intermediate-long-term care center were evaluated. Of them, 39 were excluded because they were unable to perform a clinical interview, needed to diagnose depression. Of the excluded patients, 18 had aphasia, 7 showed severe cognitive impairment: their mini mental state examination (MMSE) score < 14, and 14 collaborated very poorly. Thus 37 patients were analyzed, mean age was 83 +/- 0.86 years (30 women and 7 men). Diagnostic categories were: neurological 16 patients (43.2%), fractures/orthopedics 6 (16.2%), pulmonary/cardiology 5 (13.5%) and others 10 (27.1%). The mean Barthel index was 57.0 +/- 31.6 and mean MMSE score was 21.1 +/- 4.3. The observational scale (OS) designed with six items, was applied to all patients. Each item was scored as never (0 points), sometimes (1 point) and always (2 points). Thus total OS score ranged from 0 to 12. Two observers, who knew the patients (nurses), applied the OS. A trained geriatrician, using the 15-item geriatric depression scale (GDS) performed detection of depressive symptoms. There were 15 patients (40.5 %) with depression on the GDS. OS scale score with a cutoff point of 5 or more was present in 13 patients; nine of them had depression (69.2 %). In the remaining 24 patients with an OS score < 5, depression was present only in 6 cases (25%) (chi2 = 6.844; p < 0.01). The OS >/= 5, in the present study, obtained a sensitivity of 60 %, a specificity of 81 %, a positive predictive value of 69 %, and a negative predictive value of 75 %.We concluded that (i) the OS has been useful for identifying depressive symptoms with an acceptable sensitivity and specificity, and (ii) the OS may be an alternative to detect depression in patients who are unable to perform a clinical interview.

Aged↗

[Ocular presentation in Wegener granulomatosis].

CASE REPORT: A 71 year-old female presented with bilateral conjunctivitis, scleritis and peripheral ulcerative keratitis. Ancillary tests showed presence of anti-neutrophil cytoplasmic antibodies, with diffuse granular cytoplasmic immunofluorescence staining (ANCAc). Conjunctival biopsy showed necrotizing vasculitis in small vessels. Diagnosis of Wegener Granulomatosis (WG) was established and upper respiratory affection detected. Treatment with megadoses of cyclophosphamide and corticoids was initiated and remission of the disease was obtained. DISCUSSION: WG is a potentially lethal systemic vasculitis in which ocular involvement may be the first clinical presentation. Scleritis and peripheral ulcerative keratitis indicate systemic involvement, highlighting the importance of prompt diagnosis and treatment.

Aged↗

[Ocular Behçet disease. Retrospective study].

OBJECTIVE: To study clinical features, visual prognosis and response to immunosuppressive drugs in patients with ocular Behçet Disease (BD). PATIENTS AND METHODS: clinical data of 17 patients (33 eyes) were retrospectively reviewed from May 1996 to May 2003. RESULTS: The male/female ratio was 12/5. The commonest manifestations were oral ulceration (100%) and skin lesions (88%). Anterior uveitis was present in 59%, posterior uveitis was in 76% and panuveitis was in 88.1%. Visual acuity improved in 11 (33.3%) eyes, remind stable in 18 (54.5%) eyes and four (12.1%) eyes lost two or more lines. Main drug therapy consisted of colchicine and cyclosporine (59%). Seven patients had received three drugs simultaneously. CONCLUSIONS: BD can lead to an irreversible visual loss; however, the visual prognosis is good (85%) if immunosuppressor treatment is implemented.

Adolescent↗

Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease.

BACKGROUND: Parasympathetic dysautonomia is an established feature of advanced Chagas cardiomyopathy. However, in the absence of cardiac involvement, the presence of vagal dysfunction remains controversial. In a cross-sectional study, we compared patients with Chagas disease without cardiac involvement and healthy individuals by three different methods to determine whether vagal dysfunction is present in the early phase of Chagas disease. METHODS: Sixty-one patients with Chagas disease without cardiac involvement and 38 controls were submitted to respiratory sinus arrhythmia test and 24-hour Holter monitoring. Vagal heart influences were assessed by the expiratory/inspiratory (E/I) ratio, time-domain indexes of heart rate variability (HRV), and by the quantification of a 3-dimensional return map. RESULTS: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. Compared with the control group, patients with Chagas disease had significantly lower values of the E/I ratio (mean +/- SD: 1.38 +/- 0.02 and 1.25 +/- 0.02, P <.004) and short-term indexes of HRV (median [interquartile range]-rMSSD: 23 [18-27] and 17 [13-23], P =.00; pNN50: 11 [7-17] and 6 [2-12], P =.00). P(3), a beat-to-beat HRV index derived from the 3-dimensional return map, also was significantly reduced in the Chagas disease group (mean +/- SD: 118 +/- 5 vs 100 +/- 4, P =.00). None of these indexes of vagal heart control were significantly correlated with left ventricular function or to the presence of esophageal radiologic abnormalities. CONCLUSION: Parasympathetic dysautonomia is an independent and early phenomenon in Chagas disease and may precede left ventricular systolic dysfunction.

Adolescent↗

Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules.

This study attempted to evaluate and compare the role of various B cell-specific markers for anti-viral immune responses in mouse strains lacking molecules belonging to the B cell receptor (BCR) complex (IgM, Ig alpha and C(kappa)), the co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine kinase (Btk)] or the transcription factors (OBF-1). These mice were tested in two model infections [vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T cell functions were within normal ranges. In contrast, OBF-1(-/-) mice were partially protected and mb-1(delta c/delta c) mice not at all protected against VSV infection, a virus that is controlled virtually exclusively by neutralizing antibodies. Susceptibility to VSV infection was correlated with structural defects in the spleen: absence of mature B cells and follicles with marginal zone macrophages and absence of germinal centers with follicular dendritic cells correlated with lack or substantial reduction of protective IgM and IgG responses respectively. The lack of kappa light chain did not affect the neutralizing response, indicating that it could easily be replaced by the lambda chain. Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling molecule Btk had modulating effects, but did not increase susceptibility to VSV or LCMV. Our findings suggest that there are crucial molecules for B cell activation at the beginning (BCR complex) and the end (transcription) of the signaling cascade, whereas fine-tuning factors modulating the response in between exhibit considerable functional overlap.

Agammaglobulinaemia Tyrosine Kinase↗

A negative regulatory role for Ig-alpha during B cell development.

The development of B cells requires the expression of an antigen receptor at distinct points during maturation. The Ig-alpha/beta heterodimer signals for these receptors, and mice harboring a truncation of the Ig-alpha intracellular domain (mb-1(delta(c)/delta(c)) have severely reduced peripheral B cell numbers. Here we report that immature mb-1(delta(c)/delta(c) B cells are activated despite lacking a critical Ig-alpha-positive signaling motif. As a consequence of abnormal activation, transitional immature IgMhighIgDlow B cells are largely absent in mb-1delta(c)/delta(c) mutants, accounting for the paucity of mature B cells. Thus, Ig-alpha cytoplasmic tail truncation yields an antigen receptor complex on immature B cells that signals constitutively. These data illustrate a role for Ig-alpha in negatively regulating antigen receptor signaling during B cell development.

Animals↗

Ig-alpha cytoplasmic truncation renders immature B cells more sensitive to antigen contact.

To study the function of Ig-alpha in the selection of autoreactive B cells, we have analyzed mb-1 cytoplasmic truncation mutant mice (mb-1delta(c)/delta(c)), which coexpress transgenes encoding hen egg lysozyme (HEL) and HEL-specific immunoglobulin. We demonstrate that in the presence of soluble HEL (sHEL) and dependent on the mb-1delta(c) mutation, most immature B cells bearing the HEL-specific Ig transgene undergo rearrangements of endogenous kappa light chains, resulting in loss of HEL specificity. Moreover, immature B cells from Ig-alpha mutant mice respond to BCR cross-linking with an exaggerated and prolonged calcium response and induction of protein tyrosine phosphorylation. Our data imply a negative signaling role for Ig-alpha in immature B cells.

Animals↗

Characterization of alpha1-adrenoceptor subtypes mediating vasoconstriction in human umbilical vein.

1. The present study attempted to characterize pharmacologically the subtypes of alpha-adrenoceptors mediating contractions in human umbilical vein (HUV). 2. HUV rings were mounted in isolated organ baths and cumulative concentration-response curves were constructed for the alpha-adrenoceptor agonists phenylephrine and adrenaline. Adrenaline was more potent than phenylephrine (pD2=7.29 and 6.04 respectively). 3. Isoproterenol exhibited no agonism on KCl pre-contracted HUV rings. Propranolol (1 microM) and rauwolscine (0.1 microM) did not affect the concentration-response curves to adrenaline. These results demonstrate the lack of involvement of functional beta-or alpha2-adrenoceptors in adrenaline-induced vasoconstriction. 4. The non subtype selective alpha1-adrenoceptor antagonist prazosin was evaluated on phenylephrine and adrenaline concentration-response curves. The effects of the competitive alpha1A and alpha1D-adrenoceptor antagonists, 5-methyl urapidil and BMY 7378 and the irreversible alpha1B selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline concentration-response curves. 5. The potencies of prazosin against responses mediated by adrenaline (pA2= 10.87) and phenylephrine (pA2= 10.70) indicate the involvement of prazosin-sensitive functional alpha1-adrenoceptor subtype in vasoconstriction of the HUV. 6. The potencies of 5-methyl urapidil (pA2 = 6.70) and BMY 7378 (pA2= 7.34) were not consistent with the activation of an alpha1A- or alpha1D-adrenoceptor population. 7. Exposure to a relatively low CEC concentration (3 microM) abolished the maximum response to adrenaline suggesting that this response was mediated by an alpha1B-adrenoceptor subtype. 8. We conclude that HUV express a prazosin-sensitive functional alpha1-adrenoceptor resembling the alpha1B-subtype according with the low pA2 values for both 5-methyl urapidil and BMY 7378 and the high sensitivity to CEC.

Adrenergic Agonists↗

Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification.

Mice carrying transgenic rearranged V region genes in their IgH and Igkappa loci to encode an autoreactive specificity direct the emerging autoreactive progenitors into a pre-B cell compartment, in which their receptors are edited by secondary Vkappa-Jkappa rearrangements and RS recombination. Editing is an efficient process, because the mutant mice generate normal numbers of B cells. In a similar nonautoreactive transgenic strain, neither a pre-B cell compartment nor receptor editing was seen. Thus, the pre-B cell compartment may have evolved to edit the receptors of autoreactive cells and later been generally exploited for efficient antibody diversification through the invention of the pre-B cell receptor, mimicking an autoreactive antibody to direct the bulk of the progenitors into that compartment.

Animals↗

Aberrant B cell development and immune response in mice with a compromised BCR complex.

The immunoglobulin alpha (Ig-alpha)-Ig-beta heterodimer is the signaling component of the antigen receptor complex on B cells (BCR) and B cell progenitors (pre-BCR). A mouse mutant that lacks most of the Ig-alpha cytoplasmic tail exhibits only a small impairment in early B cell development but a severe block in the generation of the peripheral B cell pool, revealing a checkpoint in B cell maturation that ensures the expression of a functional BCR on mature B cells. B cells that do develop demonstrate a differential dependence on Ig-alpha signaling in antibody responses such that a signaling-competent Ig-alpha appears to be critical for the response to T-independent, but not T-dependent, antigens.

Animals↗

A prematurely expressed Ig(kappa) transgene, but not V(kappa)J(kappa) gene segment targeted into the Ig(kappa) locus, can rescue B cell development in lambda5-deficient mice.

We generated surrogate light chain (SLC)-deficient mice carrying either a V(kappa)J(kappa)-C(kappa) transgene under the control of the kappa promoter and intron enhancer or a V(kappa)J(kappa) gene segment targeted into its physiological position. Efficient rescue of B cell development was seen in the former and partial rescue in the latter. This difference corresponded to a developmentally earlier onset of kappa chain expression from the conventional than from the targeted transgene. Thus, a kappa chain can substitute for SLC in development. However, mechanisms controlling gene expression in addition to gene rearrangements appear to restrict kappa chain expression largely to a cellular compartment into which mu chain-expressing B cell progenitors are selected with the help of the SLC.

Animals↗

Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles.

Murine CD22 (mCD22) is a B cell-associated adhesion protein with seven extracellular Ig-like domains that has 62% amino acid identity to its human homologue. Southern analysis on genomic DNA isolated from tissues and cell lines from several mouse strains using mCD22 cDNA demonstrated that the Cd22 locus encoding mCD22 is a single copy gene of < or = 30 kb. Digestion of genomic DNA preparations with four restriction endonucleases revealed the presence of restriction fragment length polymorphisms (RFLP) in BALB/c, C57BL/6, and C3H strains vs DBA/2J, NZB, and NZC strains, suggesting the presence of two or more Cd22 alleles. Using a mCD22 cDNA clone derived from the BALB/c strain, we isolated genomic clones from a DBA/2J genomic library that contained all the exons necessary to encode the full length mCD22 cDNA. Fifteen exons, including exon 3 that encodes the translation start codon, were identified. Each extracellular Ig-like domain of mCD22 is encoded by a single exon. A comparison between the nucleotide sequences of the BALB/c CD22 cDNA and the exons of the DBA/2J CD22 genomic clones revealed an 18-nucleotide deletion in exon 4 (encoding the most distal Ig-like domain 1 of mCD22) of the DBA/2J genomic sequence in addition to a number of substitutions, insertions, and deletions in other exons. These nucleotide differences were also present in a cDNA clone isolated from total RNA of LPS-activated DBA/2J splenocytes by reverse transcription-polymerase chain reaction. The Cd22 locus was mapped to the proximal region of chromosome 7, a region sytenic to human chromosome 19q, close to the previously reported loci, Lyb-8 and Mag (a homologue of Cd22). An antibody (CY34) against the Lyb-8.2 B cell marker reacted with a BHK transfectant expressing the full length mCD22 cDNA, thus demonstrating that Lyb-8 and Cd22 loci are identical. Furthermore, a rat anti-mCD22 mAb, NIM-R6, bound to sIgM+ DBA/2J B cells, confirming the expression of a CD22 protein by the Cd22a/Lyb-8a allele.

Animals↗

Identification and characterization of the murine homologue of CD22, a B lymphocyte-restricted adhesion molecule.

The human B lymphocyte-specific Ag, CD22, is a cell adhesion molecule expressed on the surface during a narrow window of B cell development, coincident with surface IgD. A ligand for CD22 has recently been identified on human T cells as the low molecular mass isoform of the leukocyte common Ag, CD45RO. CD22 has been reported to function in the regulation of both T and B cell activation in vitro. In this study, we report the isolation and expression of a molecular cDNA clone encoding the murine homologue of CD22, mCD22. Within their predicted protein sequences, murine and human sequences overall have 62% identity, which includes 18 of 20 extracellular cysteines and six of six cytoplasmic tyrosines. BHK cells transfected with mCD22 cDNA specifically adhere to resting and activated T lymphocytes and in addition bound activated, but not resting, B cells. Five Th clones were analyzed for their ability to adhere to mCD22; two Th0 clones and one Th1 clone bound CD22+ BHK transfectants, but not all T cell clones bound CD22+ cells: another Th1 clone and a Th2 clone did not. mCD22+ BHK transfectants were also specifically bound by the B cell-specific mAb, NIM-R6, demonstrating that this mAb is specific for murine CD22. Human cell lines expressing the counter-receptors for human CD22 were also examined for adhesion to the murine CD22 homologue; the epitope responsible for B cell adhesion to CD22 is conserved, whereas the T cell epitope binding to CD22 is not. The cDNA and mAb to murine CD22 will be useful for defining the in vivo function of CD22.

Amino Acid Sequence↗