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Biomedical subjects

Fernando Chaves

Publications and source records attributed to Fernando Chaves.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of changes in recent tuberculosis transmission patterns after a sharp increase in immigration.

We conducted a population-based molecular epidemiological study of tuberculosis (TB) in Madrid, Spain (2002 to 2004), to define transmission patterns and factors associated with clustering. We particularly focused on examining how the increase in TB cases among immigrants in recent years (2.8% in 1997 to 1999 to 36.2% during the current study) was modifying transmission patterns. Mycobacterium tuberculosis isolates obtained from patients living in nine districts of Madrid (1,459,232 inhabitants) were genotyped. The TB case rate among foreign-born people was three to four times that of Spanish-born people, and the median time from arrival to the onset of treatment was 22.4 months. During the study period, 227 (36.3%) patients were grouped in 64 clusters, and 115 (50.7%) of them were in 21 clusters with mixed Spanish-born and foreign-born patients. Three of the 21 mixed clusters accounted for 21.1% of clustered patients. Twenty-two of 38 (57.9%) immigrants in mixed clusters were infected with TB strains that had already been identified in the native population in 1997 to 1999, including the three most prevalent strains. Factors identified as independent predictors of clustering were homelessness (odds ratio [OR], 2.3; 95% confidence interval [95% CI], 1.2 to 4.5; P = 0.011) and to be born in Spain (OR, 1.8; 95% CI, 1.2 to 2.6; P = 0.002). The results indicated that (i) TB transmission was higher in Spanish-born people, associated mainly with homelessness, (ii) that foreign-born people were much less likely to be clustered, suggesting a higher percentage of infection before arriving in Spain, and (iii) that an extensive transmission between Spanish- and foreign-born populations, caused mainly by autochthonous strains, was taking place in Madrid.

Adolescent↗
PubMed2006

Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene.

We report a case of t(3;9)(q21;p24) in a patient with chronic idiopathic myelofibrosis (CIMF), a chronic myeloproliferative disorder (CMPD), initially detected by G-banding and fluorescent in situ hybridization (FISH) in an unstimulated culture of peripheral blood. Subsequent cytogenetic studies of bone marrow aspirates showed the presence and persistence of the same translocation. No additional cytogenetic abnormalities were found. This appears to be a unique translocation that has not been previously reported in the English literature, although both breakpoints, 3q21 and 9p24, are well known cancer-related breakpoints. The former is the mapped location of the ribophorin 1 (RPN1) gene, whereas the latter is the mapped location of the janus kinase 2 (JAK2) gene. This raises the possibility that disruption of one or both loci at the breakpoints of the presently described structural chromosomal rearrangement may be the primary event leading to the initiation and development of the hematopoietic disorder in this patient. It is not unreasonable to hypothesize that the juxtaposition of the RPN1 gene on 3q21 with the JAK2 gene on 9p24 leads to enhanced JAK2 activity. Additional studies will be needed to provide further support for or to disprove this hypothesis. To the best of our knowledge, this is the first reported case of CIMF associated with a reciprocal 3;9 translocation with the 3q21 and 9p24 breakpoints. The elucidation of the mechanism of leukemogenesis in CIMF may one day lead to successful targeted therapy in this hematopoietic disorder. It may also shed additional light on the diagnosis, prognosis and treatment of certain other cancers with similar genetic etiologies.

Chromosome Banding↗
PubMed2006

Acute lymphoblastic leukemia with 4;11 translocation analyzed by a multi-modal strategy of conventional cytogenetics, FISH, morphology, flow cytometry and molecular genetics, and review of the literature.

We report a case of acute lymphoblastic leukemia (ALL) with a 4;11 translocation. Metaphase cells and interphase nuclei derived from a routine unstimulated culture of bone marrow were analyzed using a combined strategy of G-banding and fluorescent in situ hybridization (FISH) in addition to hematopathological analysis, flow cytometry, and molecular genetics. This multimodal approach enables a successful correlation of pathology and cytogenetics to support a comprehensive diagnosis of the patient. Meaningful prognostication and appropriate therapeutic considerations are possible only when accurate diagnostic information is given. We further search and review the literature for the most up-to-date information currently available for this subtype of ALL in the constantly evolving field of molecular cytogenetics.

Bone Marrow↗
PubMed2006

Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.

The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes.

Alleles↗
PubMed2006

[Emergence of a single clone of community-associated methicillin-resistant Staphylococcus aureus in southern Madrid children].

INTRODUCTION: The observation of an increasing number of methicillin-resistant Staphylococcus aureus (MRSA) isolated from children prompted us to study the microbiological, epidemiological and clinical characteristics of these isolates. The possibility of some of them being community-acquired focused particularly our attention. METHODS: A retrospective analysis of all children with MRSA isolated at the Doce de Octubre hospital between January 2002 and June 2005 was conducted. Infections were classified as community-acquired, hospital-acquired, or health-care associated. Isolates of MRSA were studied by pulsed-field gel electrophoresis (PFGE) and SSCmec typing. The presence of the gene encoding the Panton-Valentine leukocidin was also detected by PCR. RESULTS: MRSA were isolated from 17 patients. Seven isolates (42.2%) were community-acquired, corresponding to four cases of skin or soft-tissue infections, two otitis cases and one bacteremic pyomyositis. Six of seven community-acquired isolates had the same ECP pattern (genotype D), presented a type IV SSCmec, and were LPV toxin-producing and methicillin-resistant with no other associated resistances. CONCLUSION: To our knowledge, this study shows the presence of these community-acquired MRSA strains for the first time in Spain. The evidence of an apparently clonal spreading of community-acquired MRSA infections in children has important implications for public health and treatment strategies.

Child↗
PubMed2006

[Molecular epidemiology of Listeria monocytogenes infections in a health district of Madrid in a 3-year period (2001-2003)].

INTRODUCTION: During 2003, an increase in the number of cases of listeriosis was observed in a tertiary hospital in Madrid. The objectives of this study were to review the clinical characteristics of the cases diagnosed from 2001 to 2003 and to investigate clonal relationships among the clinical isolates of Listeria monocytogenes. METHODS: A retrospective analysis was performed of all cases of listeriosis diagnosed in Hospital 12 de Octubre (Madrid) during 2001-2003. Clinical records for each patient were reviewed and all clinical isolates were compared using serotyping and pulsed-field gel electrophoresis (PFGE) with the AscI and SmaI restriction enzymes. RESULTS: A total of 18 patients were diagnosed: 4 in 2001, 2 in 2002, and 12 in 2003. The estimated incidence rates were 7.3 cases per 1,000,000 inhabitants in 2001, 3.6 in 2002 and 21.8 in 2003. The most frequent serotype during the study period was 4b (66.7%), and this serotype represented 83.3% of the cases diagnosed in 2003. PFGE yielded 12 different genotypes; one of them (PFGE type G) was common to 5 cases diagnosed in 2003. CONCLUSION: The expansion of a single clone of L. monocytogenes during 2003 partially contributed to increasing the incidence of listeriosis that year. Molecular epidemiology techniques are useful for detecting outbreaks of a possible foodborne origin and their results should promote epidemiological studies to investigate the food products involved.

Adult↗
PubMed2006

[Bordetella pertussis detection by real-time PCR, immunofluorescence and culture: prospective evaluation and molecular epidemiology].

INTRODUCTION: An increase in the incidence of pertussis has been observed in recent years. The aim of this study was to determine the usefulness of several procedures, including real-time PCR, for the laboratory diagnosis of pertussis, and to investigate clonal relationships among clinical isolates of Bordetella pertussis. METHODS: During the period of August 2002 to October 2003, nasopharyngeal swabs were collected from pediatric and adult patients with symptoms of pertussis, and contact cases. The samples were processed by culture, direct fluorescence assay (DFA), and real-time PCR. Most of the isolates were further characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: Among 121 clinical samples corresponding to 117 patients, B. pertussis was detected in 17 samples by culture (14.1%), 30 samples (24.8%) by DFA and 41 samples (33.9%) by real-time PCR. Real-time PCR diagnosed 26 and 24 more cases than culture and DFA, respectively. Seventeen clinical isolates were available for PFGE analysis, 14 collected during the study period and three in 1997, 2000 and 2001. PFGE identified 5 different genotypes, 2 of which included 8 (genotype C) and 6 (genotype E) isolates. Two of the older isolates (1997 and 2001) were identified as genotype C. CONCLUSION: Real-time PCR applied to the diagnosis of pertussis provided more positive results than DFA and culture, but the true diagnostic value of these results should be clarified. Two bacterial clones were dominant, and one of them has circulated at least since 1997.

Adolescent↗
PubMed2006

Neutrophil volume distribution width: a new automated hematologic parameter for acute infection.

CONTEXT: The number of band forms and immature neutrophils increases during acute bacterial infection. However, the determination of band counts and other neutrophil morphologic changes, such as the presence of toxic granulation, toxic vacuolization, and Dohle bodies in the cytoplasm, is labor intensive and time consuming, as it requires manual examination by an experienced medical technologist. OBJECTIVE: To investigate the value of the neutrophil volume distribution width (NDW), generated by VCS technology of the Coulter LH 750 hematology analyzer, as an additional predictor of acute infection. DESIGN: Total white blood cell count, percentage of neutrophils, and NDW data from 70 patients with positive blood cultures for bacteria and from 35 age-matched control subjects were retrospectively analyzed. RESULTS: A significant increase in the NDW was observed in the bacteremic patients compared with the controls (24.7 +/- 4.5 vs 19.0 +/- 1.5; P < .001). Such increase was observed even in patients with white blood cell counts less than 11,000/microL (23.0 +/- 5.6 vs 19.0 +/- 1.5; P < .001) or with percentages of neutrophils less than 85% (24.0 +/- 4.9 vs 19.0 +/- 1.5; P < .001). The more dramatic increases were seen in patients with leukocytosis (25.7 +/- 3.2, P < .001) or with neutrophilia (25.9 +/- 3.4, P < .001). Using an NDW cutoff of 23, a 100% specificity and a 69% sensitivity were achieved. CONCLUSIONS: As a quantitative parameter, the NDW has potential for use as an additional indicator for diagnosing acute infection.

Acute Disease↗
PubMed2005

Role of TNF-alpha, IL-1beta and IL-6 in the local tissue damage induced by Bothrops asper snake venom: an experimental assessment in mice.

The role of the cytokines TNF-alpha, IL-1beta and IL-6 in the acute local pathological effects induced by Bothrops asper snake venom was assessed in mice. Intramuscular injection of this venom induced increments in IL-1beta and IL-6 in muscle, but no elevations of TNF-alpha were detected. Pentoxifylline (PTX), a methylxanthine derivative that inhibits the synthesis of TNF-alpha, and antibodies against these three cytokines were used to assess the role of these cytokines in venom-induced effects. As a control, PTX pretreatment was effective at abrogating lethality and serum TNF-alpha increments in mice subjected to endotoxemia induced by injection of Escherichia coli lipopolysaccharide, although it did not affect the increment in IL-1beta and IL-6 in such endotoxic model. PTX failed to reduce lethality, hemorrhage, myonecrosis, dermonecrosis and edema induced by B. asper venom. Moreover, pretreatment with anti-cytokine antibodies was also ineffective at reducing venom-induced myonecrosis and hemorrhage. It is concluded that TNF-alpha, IL-1beta and IL-6 do not have a significant role in the pathogenesis of the acute local pathological effects induced by B. asper venom in mice, although this does not exclude the possibility that these cytokines play a role in other aspects of venom-induced local pathology, as well as in the reparative and regenerative responses that take place after the onset of tissue damage.

Animals↗
PubMed2005

Epidemiology and clonality of methicillin-resistant and methicillin-susceptible Staphylococcus aureus causing bacteremia in a tertiary-care hospital in Spain.

OBJECTIVES: To describe the relative proportions of nosocomial and community-onset Staphylococcus aureus bacteremia at our institution and the epidemiologic characteristics and clonal diversity of S. aureus isolates, as determined by pulsed-field gel electrophoresis (PFGE) and antimicrobial resistance patterns. DESIGN: Retrospective cohort study of all cases of S. aureus bacteremia between October 2001 and October 2002. SETTING: A 1300-bed, tertiary-care hospital. RESULTS: One hundred sixty-two unique episodes of S. aureus bacteremia were identified. Forty-three cases (26.5%) were caused by methicillin-resistant S. aureus (MRSA). Most cases of S. aureus bacteremia, whether MRSA or methicillin susceptible (MSSA), were nosocomial in origin (77.2%) or were otherwise associated with the healthcare system (16%). Only 11 (6.8%) of the cases (all MSSA) were strictly community acquired. Thirty-five unique macrorestriction patterns were identified among the 154 isolates that were typed by PFGE. Four major genotypes were defined among the isolates of MRSA, with 36 (85.7%) represented by a single PFGE type. Of the isolates within this major clone, all (100%) were ciprofloxacin resistant and 77.8% were erythromycin resistant. In contrast, the 112 isolates of MSSA comprised 31 different PFGE types, 3 of which represented 42.9% of all MSSA isolates and were associated with both nosocomial and community-onset bacteremia. CONCLUSIONS: Most cases of S. aureus bacteremia in our healthcare region are nosocomial in origin or are acquired through contact with the healthcare system and are thus potentially preventable. To preclude dissemination of pathogenic clones, it is therefore necessary to redouble preventive measures in both the hospital and the community.

Child, Preschool↗
PubMed2005

Effects of neutrophil depletion in the local pathological alterations and muscle regeneration in mice injected with Bothrops jararaca snake venom.

In order to study the role of neutrophils in the acute local pathological alterations induced by Bothrops jararaca snake venom, and in the process of skeletal muscle regeneration that follows, an experimental model was developed in mice pretreated with either an anti-mouse granulocyte rat monoclonal immunoglobulin G, which induces a profound neutropenia, or an isotype-matched control antibody. B. jararaca venom induced prominent haemorrhage and oedema, but only a moderate myonecrosis. No significant differences were observed in the extent of local haemorrhage, oedema and myonecrosis between neutropenic and control mice, suggesting that neutrophils do not play a determinant role in the acute pathological alterations induced by B. jararaca venom in this experimental model. Moreover, no differences were observed in skeletal muscle regeneration between these two experimental groups. In both the cases, limited areas of myonecrosis were associated with a drastic damage to the microvasculature and a scarce inflammatory infiltrate, with the consequent lack of removal of necrotic debris during the first week, resulting in a poor regenerative response at this time interval. Subsequently, a similar regenerative process occurred in both groups, and by 30 days, necrotic areas were substituted by groups of small regenerating muscle fibres. It is suggested that the drastic effect exerted by B. jararaca venom in the microvasculature precludes an effective access of inflammatory cells to necrotic areas, thereby compromising an effective removal of necrotic debris; this explains the poor regenerative response observed during the first week and the fact that there were no differences between neutropenic and control mice. As neutropenia in this model lasted only 7 days, the successful regenerative process observed at 30 days is associated with revascularization of necrotic regions and with a successful removal by phagocytes of necrotic debris in both groups.

Animals↗
PubMed2005

Role of embB codon 306 mutations in Mycobacterium tuberculosis revisited: a novel association with broad drug resistance and IS6110 clustering rather than ethambutol resistance.

Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.

Antitubercular Agents↗
PubMed2005

Nosocomial spread of a Staphylococcus hominis subsp. novobiosepticus strain causing sepsis in a neonatal intensive care unit.

From 2002 to 2003, 32 isolates of Staphylococcus hominis subsp. novobiosepticus (SHN) were recovered from 21 patients, 18 of whom were neonates, with 13 considered to have late-onset SHN sepsis. All isolates from neonates had an indistinguishable pulsed-field gel electrophoresis pattern. Our data support SHN as an important nosocomial pathogen in neonates.

Adolescent↗
PubMed2005

[Impact of a non-compulsory antibiotic control program (PACTA): cost reductions and decreases in some nosocomial infections].

BACKGROUND: Antibiotics account for 30% of hospital pharmacy expenses. More than 50% of the prescriptions are considered inappropriate; hence, programs devoted to optimizing the prescription of antibiotics should be developed. We present the results of a non-compulsory program for the assessment and control of antibiotic treatment in the University Hospital 12 de Octubre in Madrid. METHODS: The program was applied in the hospitalization units of six medical and surgical departments. Treatments in all patients were checked daily and recommendations were made in writing, according to previously established criteria. The program was used for 12 months and the results were compared with those of the previous 12 months. RESULTS: 1,280 treatments were reviewed and 524 recommendations were made (80% of them were accepted). There was a 13.82% reduction in the number of defined daily doses of antibiotics/100 inpatient-days. Antibiotic expenditure decreased by 65,352 euros (5,446 euros/month), implying a reduction of 1.21 euros/hospitalization-bed/day. There were no statistically significant differences in length of hospital stay or mortality between the two periods. A reduction in the incidence of Clostridium difficile diarrhea (p < 0.0001) and Candida spp. isolations (p < 0.05) was observed. CONCLUSIONS: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in length of hospital stay or mortality. There was a reduction in the incidence of some nosocomial infections. Acceptation of the program by the physicians of the departments implicated was favorable.

Anti-Bacterial Agents↗
PubMed2005

[Failure of levofloxacin therapy in two cases of community-acquired pneumonia caused by fluoroquinolone-resistant Streptococcus pneumoniae and complicated with empyema].

BACKGROUND: Community acquired pneumonia (CAP) due to Streptococcus pneumoniae is a frequent cause of morbidity and mortality. We communicate two cases of CAP with complications. In both cases levofloxacin-resistant S. pneumoniae was isolated in pleural effusion. Patient 1: A 51-year-old man who had not received previous treatment with quinolones was admitted to the hospital for CAP and initially treated with levofloxacin (500 mg/24h iv). Four days later pleural effusion developed and fluid culture isolated levofloxacin-resistant S. pneumoniae (MIC > 32 .g/ml). The outcome was favorable following chest tube placement and treatment with beta-lactam antibiotics. Patient 2: A 73-year-old man with a history of chronic obstructive pulmonary disease was admitted due to CAP and was initially treated with levofloxacin (500 mg/24 h iv). He was transferred to our hospital after 10 days of treatment with this antibiotic, following the development of pleural effusion with isolation of levofloxacin-resistant S. pneumoniae (MIC = 12 .g/ml). The patient was treated with chest tube placement and beta-lactam antibiotics with a favorable outcome. CONCLUSIONS: Patients with CAP treated empirically must be closely followed, both clinically and radiologically, to facilitate early detection of complications due to bacterial resistance to the prescribed antibiotic. Patients with CAP who have received quinolones in the weeks before the development of pneumonia should not been treated empirically with these antibiotics because of the risk of resistance development.

Aged↗
PubMed2005

Quantitative determination of neutrophil VCS parameters by the Coulter automated hematology analyzer: new and reliable indicators for acute bacterial infection.

We studied the clinical usefulness of the VCS parameters (mean channels of cell volume, conductivity, and light scatter) in reactive neutrophils for predicting acute bacterial infection, which are obtained by the Coulter LH 750 hematology analyzer (Beckman Coulter, Fullerton, CA) during automated differential counts. Peripheral blood samples from 69 patients with positive blood cultures for bacteria and 35 control subjects were studied. We observed a significant increase in the mean channel of neutrophil volume (MNV) from septic patients compared with control subjects (156+/-13.5 vs 143+/-4.8; P<.001). The mean channel of neutrophil light scatter was decreased significantly in patients (140+/-10.1 vs 146+/-7.3; P=.002). An elevation of the MNV was associated with a higher WBC count and percentage of neutrophils and was present even in patients who did not have leukocytosis or neutrophilia. With a cutoff of 150 for the MNV, a specificity of 91% and sensitivity of 70% were achieved. As a quantitative, objective, and more sensitive parameter, we believe that the MNV has a potential to be an additional indicator for acute bacterial infection.

Acute Disease↗
PubMed2004

Molecular characterization of resistance to mupirocin in methicillin-susceptible and -resistant isolates of Staphylococcus aureus from nasal samples.

A total of 15 of 101 (14.8%) nasal methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibited mupirocin resistance (Mup(r)) compared with 1 of 154 (0.6%) methicillin-susceptible Staphylococcus aureus isolates. A total of 14 (93%) isolates exhibiting high-level Mup(r) belonged to a single clone. Horizontal plasmid transfer and transmission of Mup(r) strains contribute to a high incidence of Mup(r) MRSA at our institution.

Anti-Bacterial Agents↗