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Biomedical subjects

A Soto

Publications and source records attributed to A Soto.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2005

Intraspecific and interspecific genetic and phylogenetic relationships in the genus Populus based on AFLP markers.

Although Populus has become the model genus for molecular genetics and genomics research on forest trees, genetic and phylogenetic relationships within this genus have not yet been comprehensively studied at the molecular level. By using 151 AFLP (AFLP is a registered trademark of Keygene) markers, 178 accessions belonging to 25 poplar species and three interspecific hybrids were analyzed, using three accessions belonging to two willow species as outgroups. The genetic and phylogenetic relationships were generally consistent with the known taxonomy, although notable exceptions were observed. A dendrogram as well as a single most parsimonious tree, ordered the Populus sections from the oldest Leuce to the latest Aigeiros, a pattern consistent with their known evolutionary relationships. A close relationship between Populus deltoides of the Aigeiros section and species of the Tacamahaca section was observed and, with the exception of Populus wilsonii, between the species of the Leucoides, Tacamahaca, and Aigeiros sections. Populus nigra was clearly separated from its consectional P. deltoides, and should be classified separately from P. deltoides. The AFLP profiles pointed out to the lack of divergence between some species and revealed that some accessions corresponded with interspecific hybrids. This molecular study provides useful information about genetic relationships among several Populus species and, together with morphological descriptions and crossability, it may help review and update systematic classification within the Populus genus.

Cluster Analysis↗
PubMed2005

Incorporation of low molecular weight biocides into polystyrene-divinyl benzene beads with controlled release characteristics.

Triclosan and phosphonium salt biocides have been separately incorporated into polystyrene-divinylbenzene (PS-DVB) beads by suspension polymerization. Ultraviolet (UV) absorption measurements have been used to monitor the release of these low molecular weight biocides out of the PS-DVB beads immersed in water-ethanol mixtures and in physiological saline. The release of the biocide agents is strongly dependent on either the DVB or/and the antimicrobial composition ratio in the beads. An increase of biocide incorporation in the PS/DVB beads was accompanied by a corresponding enhancement of its concentration in liquid mixtures. On the contrary, higher cross-linking densities hindered the biocide migration out of the beads by diminishing its release rate into either the aqueous ethanol solutions or the natural serum. Moreover, Fourier transform Raman (FT-Raman) spectra and Attenuated Total Reflectance Infrared (ATR-FTIR) measurements of the PS-DVB-Triclosan and PS-DVB-phosphonium salt beads, before and after their immersion in water-ethanol solutions, gave a similar qualitative evidence of the biocide release.

Anti-Infective Agents, Local↗
PubMed2005

Gene flow and hybridisation in a mixed oak forest (Quercus pyrenaica Willd. and Quercus petraea (Matts.) Liebl.) in central Spain.

Oaks are long-standing models for the study of gene flow and hybridisation. Temperate (Quercus petraea) and sub-Mediterranean (Quercus pyrenaica) oaks coexist in central Spain, showing remarkable differences in population size and structure. Q. petraea has a scattered distribution in central Spain, where it is at one of the southernmost limits of its range, and forms low-density stands; in contrast, Q. pyrenaica is widespread in the region. We selected a mixed population of the two species ( approximately 13 ha, 176 adults and 96 saplings) to compare the patterns of gene flow within each species and the extent of introgression between them. Using five nuclear microsatellite markers, we performed a parentage analysis and found considerable immigration from outside the stand ( approximately 38% for Q. petraea and approximately 34% for Q. pyrenaica), and estimated average seed-dispersal distances of 42 and 14 m for Q. petraea and Q. pyrenaica, respectively. Introgression between species was also estimated using our microsatellite battery. First, we developed a multivariate discriminant approach and, second, we compared our results with a widely used clustering method (STRUCTURE). Both analyses were consistent with a low level of introgression between Q. petraea and Q. pyrenaica. Indeed, only 15 adult trees, approximately 8.5%, were identified as putative hybrids when both methods of analysis were combined. Hybrids may be most common in contact zones due merely to physical proximity.

Gene Flow↗
PubMed2004

The usefulness of computerized dynamic posturography for the study of equilibrium in patients with Meniere's disease: correlation with clinical and audiologic data.

The use of computerized dynamic posturogaphy (CDP) in the evaluation of patients with balance alterations not only allows quantification of the subject's capacity to maintain a stable centre of gravity, but also analysis of the degree to which the subject is able to use different types of sensory information. The present study investigated the possible use of CDP for clinical staging of vestibular diseases, specifically Meniere's disease (MD). We applied CDP sensory organization tests to 75 patients with definitive MD (AAO-HNS 1995 criteria). A total of 98 CDP sessions were included in the analysis, which focused on four CDP parameters specifically related to vestibular function (condition-5 score, condition-6 score, overall balance score, and VEST, a measure of the relative importance of vestibular information for maintenance of balance). We found a statistically significant relationship between audiometric hearing threshold and CDP scores, especially in patients with audiometrically advanced disease. In addition, CDP scores showed statistically significant variation with time elapsed since the last typical vertigo attack, suggesting that patients can be usefully grouped into three MD activity-level categories: recent post-attack (less than 1 week since last vertigo attack), late post-attack (1 week - 60 days since last attack), and inactive MD (more than 60 days since last attack). On the basis of these results, we propose expected ranges for each of the four CDP parameters in each of the three MD activity-level categories, allowing staging in terms of balance and posture. This staging system complements existing staging systems (based on audiometric criteria, and on subjective assessment of the severity of vertigo attacks and their implications for quality of life).

Adult↗
PubMed2004

Excitotoxic insults to the optic nerve alter visual evoked potentials.

Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin kainate a subcutaneously implanted osmotic pump which delivered the toxin through a cannula onto the optic nerve. Records of VEPs were obtained before pump implantation and at 1, 3 and 7 days post-implantation, and weekly evaluated thereafter for up to 4 months. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and profile after the lesion as well as in comparison to those generated in control animals infused with vehicle. Histological examination of the damage caused by the excitotoxic insult showed that large areas of the optic nerve were demyelinated and their axons distorted. These observations were confirmed and extended by immunohistochemical analyses using markers to neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The results of the present paper indicate that the consequences of excitotoxicity in the optic nerve share functional and morphological alterations which are found in demyelinating disorders. In addition, this experimental paradigm may be useful to evaluate the functional recovery of demyelinated optic nerves following various repair strategies.

Animals↗
PubMed2004

[Evaluation of individual risk and mortality related factors in acute renal failure].

OBJECTIVES: To evaluate the Individual Severity Score (ISS) as a predictor of mortality in patients with acute renal failure (ARF) and to determine mortality associated factors. METHODS: Clinical records of patients with de diagnosis of ARF at the Hospital Arzobispo Loayza (HAL) of Lima (Perú) between the years 1995 and 2000 revised. The optimal cut point for sensitivity and specificity of the ISS was assessed using ROC curve analysis. RESULTS: 128 clinical records of patients with ARF were revised. The mortality rate was 10,94 % (14/128). Patients who died were significatively older and showed more frequently hypotension, jaundice, need of mechanical ventilation and coma. The optimal cut point for the ISS was 0,74 (sensitivity of 71% and specificity of 100%). The area under the curve value was 0,91 (CI95 0,81-1,03). CONCLUSION: The ISS was shown to be a cheap, easy clinical tool with an elevated discriminant ability in the study population. Mortality associated factors were similar as previously reported.

Acute Kidney Injury↗
PubMed2003

Pancreatic ascites: study of therapeutic options by analysis of case reports and case series between the years 1975 and 2000.

OBJECTIVE: Because of the low incidence of pancreatic ascites, only case reports and case series have been published, and no randomized controlled trials have been performed to find out which is the best therapeutic approach. The aim of this study was to evaluate the utility of the different treatments for pancreatic ascites by a thorough review of all case reports described in the literature in which an independent analysis of the efficacy of the treatment administered to each patient is possible. METHODS: We conducted an analysis of all case reports and case series of pancreatic ascites published between 1975 and 2000 in which clinical data of every patient could be identified individually. A total of 139 cases were studied. Clinical characteristics, treatments administered, and response to therapy of every patient were registered. Conservative therapy included drainage of ascitic fluid, total parenteral nutrition and diet, and somatostatin analogues. Interventional therapy was either endoscopic or surgical. RESULTS: After multivariate analysis, the only treatments related to success were surgery (adjusted OR = 8.2, 95% CI = 3.0-22.9) and transpapillary stent (adjusted OR = 7.3, 95% CI = 0.8-62.9). No significant relationship was found between failure or death and the use of other treatments, age, sex, year of publication, underlying disease, site of leakage, or serum amylase levels. The apparent lack of effect of somatostatin analogues could be attributed to the small number of cases and the heterogeneity of the dosages. CONCLUSIONS: Conservative therapy is not advisable for pancreatic ascites because of the high proportion of failures. Interventional therapy with surgery or transpapillary stent has a positive effect in the clinical outcome.

Adolescent↗
PubMed2003

A prediction rule to identify allocation of inpatient care in community-acquired pneumonia.

The current authors developed a new prediction rule based on the five risk classes defined by the Pneumonia Severity Index to identify allocation of inpatient care in community-acquired pneumonia. The decision to hospitalise in low-risk classes (I-III) was unquestionable, if the presence of one or more of the following were evident: arterial oxygen tension <8.0 kPa (60 mmHg), shock, decompensated coexisting illnesses, pleural effusion, inability to maintain oral intake, social problem, and lack of response to previous adequate empirical antibiotic therapy. The results at 18 months after implementation of this new prediction rule are reported in a series of 616 patients. The mortality rate was 0.5% in 221 patients treated as outpatients versus 8.9% in 395 patients treated as inpatients. Specific additional criteria for hospitalisation included in the prediction rule were present in 106 of the 178 low-risk patients treated as inpatients, whereas in the remaining 72, the decision to hospitalise was apparently unjustified by the prediction rule. These 72 patients showed a better outcome (significantly shorter hospitalisation, days on intravenous antibiotics, mortality, and complicated course) than high-risk patients and low-risk patients who met the additional specific criteria for deciding hospital admission. Therefore, admission in these low-risk patients might have been avoided by strict adherence to the new prediction rule. Another relevant finding was that the Pneumonia Severity Index alone did not identify all patients who needed to be admitted to the hospital.

Adult↗
PubMed2001

Antimicrobial peptides isolated from skin secretions of the diploid frog, Xenopus tropicalis (Pipidae).

Seven peptides (XT-1-XT-7) with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions of the diploid clawed frog, Xenopus tropicalis. Structural characterization of the peptides demonstrated that amino acid sequence similarity to antimicrobial peptides previously isolated from Xenopus laevis was low, suggesting that the species are not closely related phylogenetically. Peptides XT-5 and XT-3 are probably the orthologs of X. laevis peptide glycine-leucine amide (PGL(a)) and the N-terminal spacer region of prolevitide, respectively. XT-1, XT-6 and XT-7 show limited structural similarity to the spacer region of X. laevis procaeruleins and the paralogs XT-2 and XT-4 are similar to corresponding regions of proxenopsin. Orthologs of the magainins were not identified. The C-terminally alpha-amidated peptide XT-7 (GLLGPLLKIAAKVGSNLL.NH2) showed the lowest minimum inhibitory concentrations against reference microorganisms (Staphylococcus aureus 5 microM, Escherichia coli 5 microM, and Candida albicans 40 microM) and was also active against clinical isolates of methicillin-resistant S. aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus group C, Shigella sonnei, Pseudomonas aeruginosa and Enterobacter cloacae. The peptide was, however, hemolytic against human erythrocytes (50% lysis at 70 microM). Circular dichroism studies showed that XT-7 has a random structure in aqueous solution, pH 7.0 but adopts an alpha-helical conformation in the presence of 50% trifluoroethanol. Decreasing the cationicity of XT-7 either by replacement of the C-terminal CONH2 group by COOH or by deletion of the Lys(8) residue produced analogs with greatly (>10-fold) decreased antimicrobial potencies.

Amino Acid Sequence↗
PubMed2001

Bioequivalence of allopurinol and its metabolite oxipurinol in two tablet formulations.

OBJECTIVE: To test for the bioequivalence of two allopurinol 300 mg tablet formulations (generic allopurinol (Normon) and Zyloric tablets). METHOD: A single dose study was carried out in 24 healthy volunteers with a two-sequence, crossover block-randomized design. Blood samples were taken prior to each administration and at 19 points within 72 h after the dose. Plasma concentrations of allopurinol and oxypurinol were determined by HPLC. The pharmacokinetic parameters Cmax and Tmax were obtained directly from plasma allopurinol and oxypurinol concentrations. ke was estimated by log-linear regression and AUC was calculated by the linear trapezoidal rule for both allopurinol and oxypurinol. The pharmacokinetic parameters AUC and Cmax were tested for equivalence after log-transformation of data. Differences of Tmax were evaluated by a non-parametric test. The 90% standard confidence intervals of the mean values for the test/reference ratios were for AUC and for Cmax, within the acceptable bioequivalence limits of 0.80-1.25 for both allopurinol and oxypurinol. CONCLUSION: The two formulations are bioequivalent and therefore interchangeable.

Adult↗
PubMed2001

Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow-up by PCR.

Patients suffering from Chagas' disease, as determined by positive serological results, were tested for further evidence of Trypanosoma cruzi infection by xenodiagnosis and PCR. The patients included 67 children aged from 0 to 10 years and 75 adults. All children were positive by PCR on their pre-therapy sample, while only 69% of the seropositive adults and none of the 78 seronegative control adults were PCR positive. Xenodiagnosis was positive in 79% of the children, but only in 21% of the adults. A group of 66 children was treated with nifurtimox, and followed up every 3 months during the first year and every 6 months during the second and third year post-therapy, by PCR, xenodiagnosis and serology. We concluded that PCR was the most effective test to monitor children for 3 years post-chemotherapy, when all the cases converted from positive to negative. Conventional serology, however, remained positive after that period in most cases. In contrast, conversion to negative xenodiagnosis occurred very early after treatment.

Adult↗
PubMed2001

Monitoring butocarboxim resistance of the woolly whitefly (Homoptera: Aleyrodidae) in citrus from Valencia, Spain.

Glass vials coated internally with an insecticide were used as a resistance monitoring technique for testing field populations of the woolly whitefly, Aleurothrixus floccosus (Maskell), collected from citrus. The distribution of resistance to the insecticide butocarboxim in citrus orchards from Valencia (Spain) during 1993 and 1994 was determined by means of this technique. Adults resting on citrus shoots were captured with a portable vacuum cleaner and introduced into the vials. The technique provides control mortality of <25% when assessed 7 h after the insects are captured. In 21 populations tested, LC50s ranged from 1.8 to 42.3 mg/ml. This represents resistance ratios >20-fold among populations. Lower slopes of the concentration-mortality line were found in whitefly populations that exhibited a low level of the LC50. Resistance was widespread in the Valencia areabut spatially irregular, with nearby orchards occasionally showing wide differences in resistance levels. The levels of resistance to butocarboxim obtained with this technique closely matched the field efficacy of the insecticide. This residue bioassay provides a convenient and rapid method to monitor insecticide resistance in A. floccosus populations.

Aldicarb↗
PubMed2001

Gender differences in the disposition of metronidazole.

OBJECTIVE: Gender is usually considered to be one of the factors influencing disposition of drugs, but the evidence available is sometimes conflicting and information for a large number of frequently used drugs is lacking. An evaluation of sex differences in the disposition ofmetronidazole was carried out during a bioequivalence study. SUBJECTS AND METHODS: Twenty-four volunteers (12 males and 12 females) were included in an open, single-dose, two-sequence, crossover randomized trial with a one-week washout interval. All volunteers received in each period, a single 250 mg dose of one of the two study formulations of metronidazole. Venous blood samples were collected immediately before and at 15 time points in an 48-hour interval after drug administration; metronidazole concentrations were determined by HPLC. Non-compartmental pharmacokinetic analysis was performed and log-transformed AUC(0-infinity) and Cmax were tested for bioequivalence. Sex differences were evaluated by means of a 4-factor (sex, sequence, treatment and period) ANOVA. RESULTS: The studied formulations were found bioequivalent according to international standards: average 90% confidence interval for AUC(0-infinity) was 98 to 104 and for Cmax 93 to 115. After correction for the administered dose/kg, AUC was about 12% lower in females than in males (p = 0.0388) and, therefore, a higher calculated oral Cl/kg was found in females. Apparent distribution volume, after correction for weight, was significantly higher in males (p = 0.0019). Metronidazole half-life and MRT were shorter in females than in males (p - 0.0014 and p = 0.0002, respectively). CONCLUSIONS: Data obtained in this study suggest that metronidazole clearance in females is about 12% higher than in males although these differences are probably of no clinical relevance.

Adult↗
PubMed2001

[Inverted metamorphopsia: an alteration in the perception of a special situation of objects].

OBJECTIVES: This study describes the characteristics of six patients who consulted because of episodes of perceptive alteration of extrapersonal space consisting in an inversion of the situation of objects although without changes in shape or size (inverted metamorphopsia). PATIENTS: Six patients (4 males and 2 females) who presented episodes of inverted metamorphopsia were studied: 4 referred right-left inversion (axial plane), 1 upwards-downwards (saggital plane) and 1 inclination of environment (clockwise movement). None had any alteration in the perception of their own bodies during the episodes which lasted from 3 minutes to 1 hour, reporting from 1 to 40 episodes. The most notable antecedents were: traumatism and forced cervical posture (2), arterial hypertension (3), migraine (2), hyperlipemia (2) and protuberantial ischemia (1). RESULTS: Intercritical neurologic exploration was normal. MR study showed leukoaraiosis (4), protuberantial paramedian infarctions (1) and was normal in one case of basilar migraine. Study of vestibular function (performed in 4 cases) did not show alterations. Three patients received antiepileptic drugs (1 carbamazepine and 2 gabapentin) with favorable response. CONCLUSIONS: Inverted metamorphopsia is a paroxistic phenomenon which transduces a dysfunction of the posterior parietal cortex or its afferences (propioceptive, vestibular, retinian). The causes may be multiple (traumatism, migraine, ischemia). Antiepileptic drugs may have a therapeutic role in the cases with multiple episodes.

Adult↗
PubMed2001

Frequency and clinical significance of myocardial ischemia detected early after coronary stent implantation.

UNLABELLED: A high number (30%-50%) of reversible defects have been detected early after coronary balloon angioplasty. Inadequate luminal enlargement despite a good angiographic appearance has been suggested as a possible mechanism of these perfusion abnormalities, and some reports have shown better coronary flow reserve after coronary stent implantation than after balloon dilatation. The primary objective of this study was to evaluate the frequency of early ischemic defects detected by maximal exercise (plus dipyridamole) with (99m)Tc-tetrofosmin SPECT after successful coronary angioplasty with stent implantation. A secondary objective was to determine the prognostic value of these early ischemic defects. METHODS: Thirty patients without previous myocardial infarction who successfully underwent 1-vessel coronary angioplasty with stent implantation were studied. Maximal-exercise (99m)Tc-tetrofosmin myocardial SPECT, with simultaneous dipyridamole if exercise was suboptimal, was performed at 6 +/- 1 d (mean +/- SD) after percutaneous transluminal coronary angioplasty. At 8 +/- 3 mo, all patients were followed up clinically, and 77% of them underwent follow-up angiography. RESULTS: The percentage of stenosis decreased from 68.5% +/- 12.6% of luminal diameter to 9.3% +/- 8.8% after stent implantation, and minimal luminal diameter increased from 0.89 +/- 0.36 mm to 2.85 +/- 0.45 mm. Mild-to-moderate reversible myocardial defects in the territory of the dilated artery were detected in 5 patients (17%), with no angiographic or procedural differences occurring between them and patients without ischemic defects. At follow-up, the target lesion revascularization rates depending on the presence or absence of early ischemic defects were 40% and 8%, respectively (P = 0.18). Angiographic restenosis occurred in 3 of 4 patients who had early ischemic defects and underwent follow-up angiography and in 3 of 19 patients who had no early ischemic defects and underwent follow-up angiography (restenosis rate, 75% and 16%, respectively; P < 0.05). CONCLUSION: Coronary angioplasty with stent implantation is associated with a 17% rate of ischemic defects early after the procedure. Patients with early myocardial perfusion defects after coronary stent implantation had a high rate of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2001

Ileal pouch-anal anastomosis for ulcerative colitis: the University of Puerto Rico experience.

OBJECTIVE: To review the experience with ileal pouch-anal anastomosis surgery for ulcerative colitis at the University Hospital. BACKGROUND: As many as 40% of patients with ulcerative colitis (UC) and 75% with Crohn's disease (CD) require some surgery for their disease. The number of patients referred to our clinics for evaluation and management of Inflammatory Bowel Disease (IBD) has risen in the past seven years. A multidisciplinary IBD service has been created at the University Hospital for the care of these patients, leading to a dramatic increase in the number of surgeries performed for IBD. Over the past decade the ileal pouch-anal anastomosis (IPAA) has emerged as the procedure of choice in most patients with ulcerative colitis requiring total colectomy for management of their disease. Even though the procedure is associated with a considerable morbidity rate, it has become very popular since it avoids the need for a permanent stoma and presumably rids the patient of disease and subsequent cancer risk. RESULTS: Twenty-five patients were identified as having IPAA for ulcerative colitis between 1993-2000. Indications for surgery were intractability and toxic megacolon. Complications were pouchitis in 11/25 (44%), anastomotic stricture in 6/25 (24%), small bowel obstruction in 4/25 (16%), and pouch failure in 2/25 (8%). Other complications included wound abscess in 1/25 (4%), and sexual dysfunction in 1/25 (4%) patients. There was no mortality; the patients' quality of life was rated as greatly improved in 14 of 17 patients interviewed (82.4%) and 16 of 17 said they would recommend the surgery to others (94.1%). CONCLUSIONS: The results of IPAA surgery, morbidity, mortality, and patient satisfaction in our series were similar to other centers around the world.

Adolescent↗