Biomedical subjects
Publications and source records attributed to M Fuentes.
Studies assessing the risk of congenital malformations associated with the treatment of asthma during the first trimester of pregnancy are few, have limited power and support continuation of treatment.
Allele and genotype frequencies for eight DNA polymorphisms (HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQalpha) were determined in a population sample of Aymara Indians from Bolivia using PCR. No deviations of the observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the systems studied. Significant differences in the allele frequencies were found between the Aymara and Quechua populations only for HUMVWA31A, which suggests a certain degree of genetic differentiation between the two populations.
BACKGROUND: Cyclooxygenase (COX) converts arachidonic acid in prostanoids. COX exists in two isoforms, COX-1 is the constitutive whereas COX-2 is the inducible isoform. The regulation of COX-1 and COX-2 expression in nasal mucosa has not been previously reported. AIM: We studied expression and regulation by cytokines and corticosteroids of COX-1 and COX-2 in human nasal mucosa. Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for COX-1 and COX-2 expression by semiquantitative competitive PCR and Western blot. METHODS: Explants were incubated with pro-(IFNgamma, IL-1beta, and TNF-alpha) and anti(IL-10) inflammatory cytokines and dexamethasone. The mechanisms which regulate COX-2 mRNA expression were studied using inhibitors of translation (Actinomycin D) and transcription (Cicloheximide). RESULTS: The baseline expression of COX-2 mRNA was higher than COX-1 mRNA. Once in culture, there was a slight spontaneous up-regulation of COX-1 and a strong COX-2 mRNA and protein up-regulation. The incubation of nasal explants with pro-inflammatory cytokines increased the expression of COX-2 mRNA and protein, from 1 to 24 h of incubation in a dose-related manner. The regulation of these effects occurred at both transcriptional and post-transcriptional levels. Dexamethasone and IL-10 abrogated cytokine-induced COX-2 mRNA and protein expression. Pro-inflammatory cytokines, dexamethasone and IL-10 had no effect on COX-1 mRNA expression. CONCLUSIONS: As prostanoids have important regulatory effects on the immunologically mediated inflammatory responses, our findings throw some light on the mechanisms that regulate the enzymes which produce these metabolites in the human airway.
Daily data for fine (< 2.5 microns) and coarse (2.5-10 microns) particles are available for 1995-1997 from the U.S. Environmental Protection Agency (EPA) research monitor in Phoenix, AZ. Mortality effects on the 65 and over population were studied for both the city of Phoenix and for a region of about 50 mi around Phoenix. Coarse particles in Phoenix are believed to be natural in origin and spatially homogeneous, whereas fine particles are primarily vehicular in origin and concentrated in the city itself. For this reason, it is natural to focus on city mortality data when considering fine particles, and on region mortality data when considering coarse particles, and most of the results reported here correspond to those assignments. After allowing for seasonality and long-term trend through a nonlinear (B-spline) trend curve, and also for meteorological effects based on temperature and specific humidity, a regression of mortality was performed on PM using several different measures for PM. Based on a linear PM effect, we found a statistically significant coefficient for coarse particles, but not for fine particles, contrary to what is widely believed about the effects of coarse and fine particles. An analysis of nonlinear pollution-mortality relationships, however, suggests that the true picture is more complicated than that. For coarse particles, the evidence for any nonlinear or threshold-based effect is slight. For fine particles, we found evidence of a threshold, most likely with values in the range of 20-25 micrograms/m3. We also found some evidence of interactions of the PM effects with season and year. The main effect here is an apparent seasonal interaction in the coarse PM effect. An attempt was made to explain this in terms of seasonal variation in the chemical composition of PM, but this led to another counterintuitive result: the PM effect is highest in spring and summer, when the anthropogenic concentration of coarse PM is lowest as determined by a principal components analysis. There was no evidence of confounding between the fine and coarse PM effects. Although these results are based on one city and should be considered tentative until replicated in other studies, they suggest that the prevailing focus on fine rather than coarse particles may be an oversimplification. The study also shows that consideration of nonlinear effects can lead to real changes of interpretation and raises the possibility of seasonal effects associated with the chemical composition of PM.
The aim of this study was assessment of the usefulness of laparoscopy in the diagnosis and treatment of the adult nonpalpable testicle. We reviewed retrospectively the case notes of five adult patients with cases of impalpable testis that were evaluated and treated laparoscopically in our institutions. All five patients had unilateral nonpalpable testicles. The mean age of the patients was 36.5 years (+/- 5 years). Laparoscopy defined the intraabdominal anatomy accurately in all cases, and there were no laparoscopic complications. Two testes were found intra-abdominally, another testicle was found lying in the inguinal canal, and the last two testes were absent. Laparoscopy is a safe and reliable method in diagnosing adults with nonpalpable testis and also allows the completion of the operative procedure during a 1-day hospital stay.
Bone is the most frequent site of metastasis in breast cancer. This causes destructive osteolytic lesions. To achieve metastasis to bone, breast cancer cells must proliferate in a new microenvironment, arrest on extracellular matrix and invade. Breast cancer cells progress in the invasive processes only if they destroy bone with the assistance of osteoclasts. In this work, we present data suggesting that MCF-7 cells, an estradiol receptor-positive cell line that exhibits modest invasive capacity, proliferate in the presence of soluble factors secreted by the osteogenic cell line SaOS-2. The cells acquire a more aggressive phenotype when cultured on an extracellular matrix produced by the same osseous cell line. Acquisition of the invasive phenotype appears to be related to the capacity of bone extracellular matrix to induce the expression of urokinase-like plasminogen activator by MCF-7 cells, which is specific for MCF-7 cells, given that MDA-231 cells, an estradiol receptor-negative and more aggressive cell line, did not show significant changes when cultured in the presence of soluble and insoluble bone factors.
OBJECTIVE: To evaluate the efficacy of intravenous cyclophosphamide pulse therapy in patients with optic neuritis associated with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Ten consecutive patients with optic neuritis due to SLE whose condition was refractory to corticosteroids and oral immunosuppressants were treated with intravenous cyclophosphamide (0.5 to 1.0 g/m2) monthly for 6 months. RESULTS: All patients had bilateral eye involvement. One eye was legally blind, and 13 eyes could see only hand movements or count fingers. Six patients had evidence of the secondary antiphospholipid antibody syndrome. Complete recovery in visual acuity occurred in 10 eyes (50%), and a partial response occurred in six eyes (30%); four eyes (20%) had no response. Complete response in the field tests occurred in eight eyes (40%), with a partial response in nine eyes (45%); no improvement occurred in three eyes (15%). CONCLUSIONS: Intravenous cyclophosphamide pulse therapy seems to be an effective treatment for optic neuritis refractory to corticosteroids, oral immunosuppressants, or both. A randomized controlled trial will be necessary to confirm our results.
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BACKGROUND: ICAM-3 has been recently identified as the third leukocyte-function associated-1 (LFA-1) ligand. ICAM-3 is expressed in eosinophils, but its regulation has not been studied. The objective of this study was to investigate the differential expression of ICAM-3 and other adhesion molecules (AM) on the surface of eosinophils. We also evaluated the effects of dexamethasone on AM expression. METHODS: Normodense eosinophils were isolated from peripheral blood and incubated with calcium ionophore A23187 (calcimycin) with and without dexamethasone. Expression of AM was assessed by flow cytometry and expressed as fluorescence mean intensity (FMI). RESULTS: Peripheral blood eosinophils constitutively expressed low levels of ICAM-1 and ICAM-2 (<10 FMI), moderate levels (10-50 FMI) of CD29 and L-selectin, and high levels (>50 FMI) of ICAM-3, LFA-1, and Mac-1. Calcium ionophore (1 microM) significantly increased Mac-1 and ICAM-1 expression at 6 and 24 h. L-selectin expression decreased at 6 and 24 h, but ICAM-2, ICAM-3, LFA-1, and CD29 expression did not show any significant change after calcium ionophore stimulation. Dexamethasone decreased ICAM-3 and increased L-selectin basal expression, and it caused a dose-related inhibition of calcium ionophore-induced ICAM-1 expression. CONCLUSIONS: These findings suggest that some AM, such as ICAM-1, Mac-1, and L-selectin, may be involved in adhesion during eosinophil activation and that glucocorticoids may prevent airway inflammation by regulating the expression of AM in eosinophils. The role of ICAM-3, a leukocyte AM highly expressed in resting eosinophils, remains to be clarified.
Exogenous prostaglandin E2 (PGE2) given by inhalation almost completely abrogates aspirin-induced asthma and the accompanying increase in cysteinyl-leukotrienes production. Cyclooxygenase (COX) may be present in cells in both constitutive (COX-1) and inducible (COX-2) forms. To increase the production of the potentially protective endogenous PGE2, COX-2 should be upregulated. We hypothesize that an abnormal regulation of COX-2 will predispose patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR). We therefore examined the expression of COX-2 messenger RNA (mRNA) in healthy nasal mucosa (n = 11) and in nasal polyps from both patients with AIAR (n = 8) and those with aspirin-tolerant asthma/rhinitis (ATAR) (n = 20). After total mRNA extraction, COX-1 and COX-2 mRNA expression were measured using a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid primers of COX-1. glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2. GAPDH were used to create PCR products that were cloned and used as internal standard controls in the competitive PCR reaction. Results are presented as mean +/- standard error of 10(6) molecules of mRNA/micrograms of total RNA. No differences in COX-1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR. However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 +/- 0. 52, sevenfold, p < 0.0001) and nasal mucosa (2.10 +/- 0.54, sixfold, p < 0.01). These findings suggest that an inadequate COX-2 regulation may be involved in AIAR.
BACKGROUND: Following extracorporeal cardiac surgery, transient myocardial dysfunction (stunning) and cellular damage may develop in relation, among other mechanisms, to the production of free radicals (FR) during reperfusion. The purpose of this study is to evaluate whether captopril (CTP), an angiotensin converting enzyme inhibitor with a thiolic group, which has been shown to be useful as an antioxidant agent both in in vitro and in vivo studies, can prevent emergence of those problems when used as pretreatment within 24 hours in patients undergoing valvular cardiac surgery. METHODS EXPERIMENTAL DESIGN: prospective and randomized study. Comparison of data pre-ischemic (pre-aortic clamping) and post-reperfusion (post-cardiac rewarming) was performed. Ejection fraction was compared pre-surgery, after surgery and after 3 months. SETTING: cardiology and cardiovascular surgery services in a general hospital. PATIENTS OR PARTICIPANTS: thirty patients who had to undergo valvular replacement surgery were randomly allocated to two similar groups, one group pretreated with captopril (CTP group, n = 15) and the other group without it (CON group, n = 15). Exclusion criteria (left ventricular ejection fraction <40%, evidence of angiographic coronary disease or prior myocardial infarction and peroperative myocardial infarction). INTERVENTION: in CTP group, the dose of captopril administered was 12.5 mg every 8 hours orally, from 24 hours before. MEASURES: using electron microscopy of myocardial biopsies taken prior to aortic clamping and post-reperfusion, a semi-quantitative analysis was performed on the degree of myocytic damage (MD), mitochondrial swelling (MS), sarcoplasmic reticulum swelling (SRS) and content in glycogen granules (GLY). Left ventricular ejection fraction was evaluated isotopically at three timepoints, preoperatively (EF1), at 2-3 days (EF2) and at 3 months (EF3). Also, analytical data were collected from the coronary sinus to determine creatine phosphokinase (CPK) and activity of the angiotensin converting enzyme (ACE). RESULTS: We noted that, in general, cellular damage resulting from valvular surgery is low, the degree of MS and SRS being lower in the CTP group. In the CTP group, however, there is a stunning phenomenon (EF1: 54.9+/-6.9%; EF2: 50.8+/-8.5%; EF3: 57.7+/-7.7%) which does not occur in the CON group (EF1: 58.0+/-8.3%; EF2: 60.8+/-10.9%; EF3: 63.0+/-9.3%). CONCLUSIONS: We conclude that the cellular damage caused during valvular replacement surgery is small, and emphasize that pretreatment with CTP further minimizes both MS and SRS; however, for reasons as yet unknown, CTP pretreatment may induce myocardial stunning, an indication that at these low rates of cellular damage, CTP has no beneficial effect, either because it is ineffective as an antioxidant agent or because FR formation has little repercussion in human beings, pointing out to the likely existence of other mechanisms that may induce an appearance of postsurgical myocardial stunning.
The technique of minimal access for mitral valve operations is commented on. A small right mediastinotomy is performed, which is a small right parasternal incision with resection of two costal cartilages. A correct exposure of the mitral valve is achieved through the right atrium and interatrial septum, allowing for adequate surgical correction.
Allele and genotype frequencies of DNA polymorphisms were determined in a population sample of Quechua (n = 113) using the polymerase chain reaction (PCR). We report data on the frequencies of HLA-DQ alpha, YNZ22, 3'ApoB, HUMTH01 and HUMVWA31A alleles and the distribution of the different genotypes. No significant deviations between observed and expected numbers were found, thus assuming the Hardy-Weinberg equilibrium.
Patients in cardiogenic shock refractory to basic medical therapy may require specialised assistance in a multispeciality environment distant to the institution where they are first admitted. In such situations, transportation of these critical patients may be difficult and involve many risks. Here we describe the case histories of two patients who underwent implantation of a paracorporeal left ventricular assist device and were transferred to specialised institutions for extended treatment. The distance of transportation was 400 km and the patients were transported by ambulance and helicopter. Some aspects of logistics and complexity of long-distance transportation are also commented on.
On the premise that it is necessary to develop antiestrogens with a higher cytotoxic component in order to reduce the risks of the development of heterogeneous malignant cell populations in breast cancer, we studied a novel series of basic diphenylethylenes, for the most part devoid of estrogenic activity, with low antiestrogenicity but much enhanced cytotoxicity compared to the reference drug tamoxifen. The main structural features associated with cytotoxicity were E isomery, substituents of five to eight carbons on the ethylene bond, and dibasicity.
INTRODUCTION AND OBJECTIVES: After the ischemia-reperfusion process in extracorporeal cardiac surgery there are, among several phenomena, some reperfusion arrhythmias which are influenced by a varied series of mechanisms. These arrhythmias have been related to the release of oxygen-derived free radicals during the first moments of reperfusion. Thus, a previous administration of free-radical scavengers might be beneficial, among which captopril has been included with good results in human studies in vitro and in animals in vivo. The aim of this study was to evaluate the influence of pretreatment with captopril on the prevention of reperfusion arrhythmias in patients undergoing valvular cardiac surgery. METHODS: 30 patients were randomly allocated to pretreatment with either captopril (CTP group, n = 15) or without captopril (CON group, n = 15). Exclusion criteria (left ventricular ejection fraction < 40%, evidence of angiographic coronary disease, prior myocardial infarction and preoperatory myocardial infarction). The dose of captopril administered was 12.5 mg every 8 hours orally, from 24 hours before surgery. A Holter register was used to analyze the ventricular arrhythmias (extrasystoles, salvos, tachycardia and fibrillation) during the first hour of reperfusion. The need for cardioversion was examined and the number of shocks needed. These events were related to changes in blood analyses from coronary sinus samples to determine creatine phosphokinase, activity of the angiotensin converting enzyme and cyclic adenosine monophosphate, before aortic clamping and after the heart was rewarmed. RESULTS: No significant differences were found in the number of ventricular arrhythmias. 60% of the patients with captopril and only 40% of the patients without it (non significant) had spontaneous defibrillation without electric shock; in those cases in which it was necessary, the number of shocks was less in the captopril group (p < 0.05). Excepting the significant correlation (p < 0.01) that we have found between ventricular fibrillation and the cyclic adenosine monophosphate increase, there is no significant correlation between the other arrhythmias and the analytical data studied. CONCLUSIONS: These data suggest that captopril, given before cardiac surgery, has little or no protector effect on reperfusion ventricular arrhythmias in extracorporeal cardiac surgery, though in patients treated with captopril there is a greater possibility of spontaneous defibrillation and fewer shocks necessary for defibrillation, without negative effects.
Several polymorphic genes including those encoding for glutathione S-transferases (GST) have been reported to be involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in humans and a possible association between the null genotype and lung cancer risk is controversial. Another polymorphic gene of the same supergene family, GSTT1, is also involved in the detoxification of some environmental carcinogens. Both genes were genotyped in (a) a group of lung cancer patients (n = 160); (b) a group of healthy smokers (n = 120); (c) a group of blood donors from the general population (n = 192). All patients and controls were Northwestern Mediterranean Caucasians. The results show that the GSTM1 null genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy smokers). The histological type most clearly modified was small cell carcinoma (frequency of 62.2%, OR: 1.91, CI: 0.78-4.69). The subdivision of the patients with one or two copies of the GSTM1 gene according to a GSTM1*A, GSTM1*B or GSTM1*A/B genotype (frequencies of 28.2%, 11.2%, 2.5% respectively) revealed no significant differences between the cases and both control groups. The frequency of the deleted GSTT1 genotype among the lung cancer patients (24%) was not significantly increased (OR: 1.08, CI: 0.57-2.05, referred to healthy smokers). The results showed that 14.4% of the patients presented homozygous deletion of both GSTT1 and GSTM1 (12.5% among healthy smokers) suggesting no potentiation between null genotypes for lung cancer risk.