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C Muñoz

Publications and source records attributed to C Muñoz.

At least 19 recordsLinked to original sources

Proposal for a supersymmetric standard model.

The fact that neutrinos are massive suggests that the minimal supersymmetric standard model (MSSM) might be extended in order to include three gauge-singlet neutrino superfields with Yukawa couplings of the type H2Lnuc. We propose to use these superfields to solve the mu problem of the MSSM without having to introduce an extra singlet superfield as in the case of the next-to-MSSM (NMSSM). In particular, terms of the type nuc H1H2 in the superpotential may carry out this task spontaneously through neutrino vacuum expectation values. In addition, terms of the type (nuc)3 avoid the presence of axions and generate effective Majorana masses for neutrinos at the electroweak scale. On the other hand, these terms break lepton number and R parity explicitly. For Dirac masses of the neutrinos of order 10(-4) GeV, eigenvalues reproducing the correct scale of neutrino masses are obtained.

Journal Article↗

Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response.

BACKGROUND: An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection. AIM: To analyse the Th1/Th2 cytokine profile in peripheral blood CD4(+) and CD8(+) T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon-alpha2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR). METHODS: Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG-IFNalpha2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non-responders. Sixteen healthy controls were analysed. The production of IL-4, IFNgamma and TNFalpha by CD4(+) and CD8(+) T cells was measured using flow cytometry, both in resting and phorbol-ester-stimulated cells. RESULTS: First three months of treatment: the synthesis of TNFalpha by phorbol-ester-stimulated-CD4(+) T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNgamma by stimulated-CD4(+) and CD8(+) T cells (P < 0.05). At the end of follow-up, a higher intracellular expression of IFNgamma by CD4(+) T cells was associated with a SVR. CONCLUSIONS: A Th1-type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNgamma and TNFalpha.

Adult↗

Prevalence and characteristics of smoking in primary healthcare workers in Iquique, Chile.

OBJECTIVE: To determine the prevalence and characteristics of the smoking habits of primary healthcare workers in Iquique, Chile. STUDY DESIGN: Cross-sectional study through a survey of all personnel working in primary health care in Iquique, Chile. METHODS: The following variables were investigated: biodemographical characteristics and aspects of smoking, knowledge of the adverse effects of smoking, and some lifestyle factors. RESULTS: Among the study population, a high prevalence of smokers was found (37%) and a further 26% were ex-smokers. The smokers were predominantly practical nurses, female, aged 25-45 years and married. The only significant relationship was between age and smoking habit (P=0.02), with smoking prevalence among younger groups being very high (56%). There was a high level of awareness about the adverse effects of smoking and its addictiveness (99 and 93%, respectively). Forty-three percent of participants had been smoking for more than 15 years, and the main reasons for smoking were 'social consumption' and 'stress' (36 and 29%, respectively). Thirty-two percent of the ex-smokers ceased smoking for discomfort or health reasons. There were no differences between smokers and ex-smokers with respect to participation in sports or working shifts. Fifty-two percent of those surveyed reported they they were annoyed when others smoked near them. CONCLUSION: This study revealed a high prevalence of smoking, particularly among practical nurses. Regarding attitudes to health, a dichotomy between knowledge and behaviour was found in this group. In pursuing the commitment to smoking cessation in healthcare personnel, a deeper review of cultural issues and motivation should be considered.

Adult↗

Molecular mapping of genes for resistance to the bean pod weevil (Apion godmani Wagner) in common bean.

The bean pod weevil (Apion godmani Wagner) is a serious insect pest of common beans (Phaseolus vulgaris L.) grown in Mexico and Central America that is best controlled by host-plant resistance available in Durango or Jalisco genotypes such as J-117. Given unreliable infestation by the insect, the use of marker-assisted selection is desirable. In the present study, we developed a set of nine molecular markers for Apion resistance and mapped them to loci on chromosomes 2, 3, 4 and 6 (linkage groups b01, b08, b07 and b11, respectively) based on genetic analysis of an F (5:10) susceptible x resistant recombinant inbred line population (Jamapa x J-117) and two reference mapping populations (DOR364 x G19833 and BAT93 x JaloEEP558) for which chromosome and linkage group designations are known. All the markers were derived from randomly amplified polymorphic DNA (RAPD) bands that were identified through bulked segregant analysis and cloned for conversion to sequence tagged site (STS) markers. One of the markers was dominant while four detected polymorphism upon digestion with restriction enzymes. The other markers were mapped as RAPD fragments. Phenotypic data for the population was based on the evaluation of percentage seed damage in replicated trials conducted over four seasons in Mexico. In single point regression analysis, individual markers explained from 3.5 to 22.5% of the variance for the resistance trait with the most significant markers overall being F10-500S, U1-1400R, R20-1200S, W9-1300S and Z4-800S, all markers that mapped to chromosome 2 (b01). Two additional significant markers, B1-1400R and W6-800R, were mapped to chromosome 6 (b11) and explained from 4.3 to 10.2% of variance depending on the season. The latter of these markers was a dominant STS marker that may find immediate utility in marker-assisted selection. The association of these two loci with the Agr and Agm genes is discussed as well as the possibility of additional resistance genes on chromosome 4 (b07) and chromosome 3 (b08). These are among the first specific markers developed for tagging insect resistance in common bean and are expected to be useful for evaluating the mechanism of resistance to A. godmani.

Animals↗

Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation.

Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients.

Adolescent↗

Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection.

BACKGROUND: First, to establish the mutations of the protoporphyrinogen-oxidase (PPOX) gene in four Spanish patients with variegate porphyria (VP). Second, study of carrier status detection in the families, including a four-generation Balearic family. Third, evaluation of the results of carrier detection screening methods. DESIGN: Blood samples of four patients and of 139 members belonging to four families, including four generations of a Balearic family were processed for mutation analysis of the 13 exons of PPOX gene. Biochemical studies were performed together (blood and faecal porphyrin analysis) and plasma fluorescence scanning for 626 nm peak emission detection. A questionnaire regarding clinical manifestations was submitted to all family members studied. RESULTS: Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077-1082insC: exon 10, and IVS6+2T-->A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checked in the carriers detected and found as not relevant or not present. Only 11 members of the 19 mutation-bearing individuals showed plasma fluorescence PV peak positivity. CONCLUSION: Demonstration of gene mutation is the most reliable means of detecting carriers in studies of variegate porphyria families. DNA analysis is the most sensitive carrier detection method and also allows transmission behaviour of the genetic defect to be established in successive generations of the affected families.

Adult↗

Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C.

OBJECTIVES: To analyze the T1/T2 cytokine profile in CD8 T cells from peripheral blood mononuclear cells from patients with genotype-1 CHC during treatment with pegylated interferon (Peg-IFN) alpha2a plus ribavirin (RBV). To correlate Th1/Th2 balance with virological response. PATIENTS AND METHODS: In this prospective longitudinal study, a total of 28 naïve genotype-1 CHC patients received Peg-IFNalpha2a (180 microg/week) plus RBV (1-1.2 g/day) for 48 weeks. All patients (mean age 45 +/- 8 years) completed treatment and follow-up: 12 (43%) achieved a sustained virological response (SVR), 13 relapsed after end of treatment (47%), and only 3 (10%) were non-responders. Sixteen healthy controls were also analyzed (mean age 39 +/- 17 years). The production of IL-4, IFNgamma, and TNFalpha by CD8 T cells was measured by intracytoplasmic detection using flow cytometry in both resting and stimulated cells with a phorbol ester. STATISTICS: Student's t test for independent values, chi2 test, and ANOVA test were used; relapsers and non-responders were joined to achieve a higher statistical power. RESULTS: At third month during treatment, phorbol ester-stimulated-IL-4 levels tend to be lower in patients who presented with SVR versus those who did not (0.97 vs 2.58; p = 0.1). No statistically significant differences were found in IFNgamma and TNFalpha levels at month 3. At EOT, the stimulated-IFNgamma production was significantly higher in patients with SVR (20 vs. 8; p < 0.05). Conversely, IL-4 production was higher in NR patients although these data did not reach statistical significance (p < 0.1). No significant differences were found in TNFalpha (14 vs. 7; p < 0.2). CONCLUSIONS: Cytokine T1 induced-response maintenance during combination treatment, measured as IFNgamma production by CD8+ T lymphocytes, is associated with SVR and suggests the replication control and later clearance of patients infected by genotype-1 HCV.

Adult↗

The value of colonoscopy to assess rectal bleeding in patients referred from Primary Care Units.

OBJECTIVES: Rectal bleeding is very common in the general population. It is produced mainly because of benign disease originating in the anus and the rectum. Our aim was to evaluate the need for colonoscopy in patients presenting with rectal bleeding. PATIENTS AND METHODS: Patients referred from Primary Care Units and complaining of rectal bleeding were included prospectively in a three-month study. All patients underwent a careful medical history along with physical examination, laboratory tests, and colonoscopy. RESULTS: 126 patients with a mean age of 49.2 years (range: 19-80) were studied. Rectal digital examination was abnormal in 75 cases (59.5%). Severe disease was encountered in 22 patients (neoplasm, angiodysplasia, and inflammatory bowel disease); 10 patients had polyps, 6 had colorectal cancer, and 6 had inflammatory bowel disease. Out of 63 patients younger than 50 years, 5 had severe disease, all of them in the form of inflammatory bowel disease. CONCLUSIONS: A neoplasm of the rectum and colon in patients younger than 50 years is a rare event. A colonoscopy must be performed in this group of patients to rule out inflammatory bowel disease.

Adult↗

Relevance of the pH probe in sleep study analysis in infants.

BACKGROUND: To establish the relationship between sleep apnoea and gastro-oesophageal reflux in infants and describe the clinical, demographic and pHmetric profile and the characteristic of the sleep polysomnography with a pH probe. METHODS: A total of 102 consecutive patients were evaluated. Parents were requested to fill out a questionnaire about symptoms and previous therapy. Gastro-oesophageal reflux was considered abnormal when the percentage of time with pH less than 4 was higher than 4% of total sleep time. RESULTS: A total of 102 infants were enrolled, 53% males. Seventy-four per cent of the infants were full-term babies. At the moment of the polysomnography, the mean age of the sample was 2.6 months. Suspicion of apnoea was the most common clinical diagnosis prior to the study. Only two infants have abnormal electroencephalogram. Mild gastro-oesophageal reflux was seen in 37 (36%) infants, while 22 (21.5%) did not have any reflux episode, and the remaining 43 (42%) infants had reflux index in the pathologic range. Only one patient had an unequivocal temporal relationship between acid oesophageal reflux and respiratory pause with oxygen desaturation. DISCUSSION: Infants with history of apnoea or acute life threatening event frequently had gastro-oesophageal reflux episodes which did not correlated with respiratory events, suggesting that gastro-oesophageal reflux and apnoea often occur in the same infant as two separate events.

Chile↗

Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites.

BACKGROUND AND AIMS: Translocation of intestinal bacteria to ascitic fluid is probably the first step in the development of episodes of spontaneous bacterial peritonitis in patients with cirrhosis. We have recently reported the detection of bacterial DNA in blood and ascitic fluid from patients with advanced cirrhosis, what we consider as molecular evidence of bacterial translocation. Several studies have shown the immunogenic role of bacterial DNA in vitro, and we hypothesised that the presence of bacterial DNA could activate the type I immune response in peritoneal macrophages from these patients, leading to greater cytokine synthesis (interleukin (IL)-2 and IL-12, tumour necrosis factor alpha, and interferon gamma) and effector molecules such as nitric oxide. METHODS: Peritoneal macrophages obtained from patients with cirrhosis and culture negative non-neutrocytic ascitic fluid were collected and characterised by flow cytometry. Inducible nitric oxide synthase, nitric oxide levels, and cytokine production were measured by immunoenzymometric assays in basal and harvested conditions according to the presence/absence of bacterial DNA. RESULTS: The ability of peritoneal macrophages to synthesise nitric oxide and levels of all cytokines were significantly increased in patients with bacterial DNA. There was a positive correlation between inducible nitric oxide synthase and nitric oxide levels. CONCLUSIONS: The presence of bacterial DNA in patients with decompensated cirrhosis is associated with marked activation of peritoneal macrophages, as evidenced by nitric oxide synthesising ability, together with enhanced cytokine production.

Aged↗

[Recurrent ischemic strokes secondary to acquired hypercoagulability in a patient with prostatic adenocarcinoma].

Hypercoagulable states are frequently associated to malignancies. We report the case of a 67 year-old patient with prostatic cancer (T3NxM1) and deep venous thrombosis, whose initial coagulation studies were normal. He was treated with acenocumarol and hormonal blockade with flutamide and leuprolerin acetate. Six months later he developed recurrent brain ischemic strokes in the territories of both median cerebral arteries, that did not respond to anticoagulant treatment. Coagulation studies, showed a procoagulant activity with a probable paraneoplastic origin. We conclude that prostatic adenocarcinoma treated with hormonal blockage may promote a complex procoagulant state leading to recurrent occlusive arterial disease, refractory to anticoagulation.

Adenocarcinoma↗

Neuroprotective properties of tianeptine: interactions with cytokines.

Tianeptine is an antidepressant with proven clinical efficacy and effects on hippocampal plasticity. Hypoxia increased lactate dehydrogenase (LDH) release from cortical neuronal cultures, and tianeptine (1, 10 and 100 microM) inhibited LDH release as efficiently as the N-methyl-D-aspartate (NMDA) antagonist, MK-801. However, tianeptine did not block apoptosis in cultured cortical neurones caused by NMDA, but reduced apoptosis when interleukin-1beta (IL-1beta) was included with NMDA. In 5-day old mice, intracerebral injection of ibotenate induced reproducible lesions in cortex and white matter. Lesion size was markedly reduced by co-administration of MK-801 (1 mg/kg i.p.) but neither by tianeptine or its enantiomers administered acutely (1, 3 or 10 mg/kg i.p.) nor by tianeptine administered chronically (10 mg/kg i.p. for 5 days). Chronic administration of IL-1beta (10 ng/kg i.p. for 5 days) prior to ibotenate injection exacerbated lesion size in cortex and white matter, and this exacerbation was prevented by chronic pre-treatment with tianeptine (10 mg/kg i.p.) or by acute administration of tianeptine (10 mg/kg i.p.) concomitantly with ibotenate. Thus tianeptine has neuroprotective effects against hypoxia in tissue culture and against the deleterious effects of cytokines in cortex and white matter, but not against NMDA receptor-mediated excitotoxicity.

Animals↗

Study of the correlation between two methods used to monitor thymoglobulin therapy in renal transplantation.

The aim of this study is to evaluate the correlation between the 2 methods used to monitor thymoglobulin therapy: the total lymphocyte count and the number of T cells. We have performed daily collections of peripherical blood samples from 24 renal grafts, recipients who were receiving thymoglobulin, including 14 cases for induction and 10 for acute rejection. Absolute lymphocyte and T-cell counts were measured in the 298 samples after administration of a dose of 1.25 mg/kg/d. The dose was omitted if the T-cell count had decreased to <10 cells/microL. The theoretical total lymphocyte count considered to omit dose was <100 cells/microL. A total of 137 doses were given according to T-cell count. We performed the comparison in 3 steps. First, we correlated values in the daily samples; second, we examined samples as a whole and third, assessed the percentage of discrepancy between the omission of the daily dose according to each method. There was a poor correlation between the methods according to sets of daily samples or the sets as a whole. The rate of discrepancy was 66%, including 121 of 216 decisions (P<.001). In conclusion, the results of the 2 methods of monitoring thymoglobulin therapy are different, and the total administered dose depends on the method used.

Antilymphocyte Serum↗

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer.

BACKGROUND: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. AIMS: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. PATIENTS AND METHODS: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. RESULTS: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p=0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p=0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p=0.02). Multivariate analysis in the complete series showed that stage (p=0.006) and lymph node metastases (> or =4 nodes, p=0.0001; 1-3 nodes, p=0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p=0.001). CONCLUSIONS: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II.

Aged↗