Biomedical subjects

M A Dominguez

Publications and source records attributed to M A Dominguez.

16 recordsLinked to original sources

PubMed2006

Risk-factors for acquisition of extended-spectrum beta-lactamase-producing Escherichia coli among hospitalised patients.

Between 1996 and 2002, 103 hospitalised patients yielding one or more clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) were identified. A significant increase was observed in the incidence of ESBL-EC colonisation or infection during the study period (1.65 episodes/100 000 patient-days in 1996 to 12.6 episodes/100 000 patient-days in 2002; p 0.01). Infection developed in 70 (68%) patients (75 episodes), with surgical site (44%) and urinary tract (17%) infections being the most frequent. Pulsed-field gel electrophoresis showed extensive clonal diversity among the isolates. A case-control study and multivariate analysis identified female gender (OR 2.1; p 0.01), use of a nasogastric tube (OR 3.5; p 0.001) and previous antibiotic therapy (OR 3.9; p < 0.001) as independent variables associated with acquisition of ESBL-EC. The study demonstrated a progressive increase in the number of ESBL-EC isolates in a non-epidemic setting. Most cases of ESBL-EC colonisation or infection occurred in hospitalised patients exposed to invasive procedures and antibiotic pressure.

Adolescent↗

PubMed2003

An outbreak of carbapenem-resistant Pseudomonas aeruginosa in a urology ward.

OBJECTIVE: To investigate an outbreak of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in a urology ward. METHODS: Patients infected or colonized with CRPA were prospectively identified by daily laboratory surveillance. Routine infection-control measures were reinforced, disinfection protocols were revised, and a surveillance program was set up, analyzing cross-transmission in the nursing ward and environment cultures from urology wards and the operating theater. CRPA isolates from clinical and environment samples were studied by pulsed-field gel electrophoresis (PFGE), following XbaI and SpeI restriction. RESULTS: From February 1998 to September 2000, 59 adult urology patients were colonized or infected by CRPA. All patients had been operated on prior to identification of the CRPA isolate and 79% of these procedures were performed in the same cystoscopy room. No patients had received prior carbapenem therapy. No cross-transmission was detected, and environment cultures from the urology ward and theater were negative except for five samples collected in the cystoscopy room. PFGE identified a single clone in the isolates from different patients and the environment samples. CONCLUSIONS: The PFGE analysis indicated that the CRPA outbreak resulted from the contamination of the cystoscopy room via an unsealed drain. The outbreak ended when the drain was sealed.

Anti-Bacterial Agents↗

PubMed2001

Differential effects of isomeric incorporation of fluorophenylalanines into PvuII endonuclease.

Incorporation of fluorine into proteins has long served as a means of probing structure and function, yet there are few studies that examine the impact of fluorine substitution, particularly at locations distant from the active sites of enzymes. The flexibility of isomeric fluorine incorporation at Phe is used to explore subtle substitution effects on enzyme activity and conformation. The unnatural amino acids o-, m-, and p-fluorophenylalanines were incorporated biosynthetically into the representative PvuII restriction endonuclease. Interestingly, m-fluoro-Phe-PvuII endonuclease exhibits very similar conformational stability to that of the native enzyme, but it exhibits a reproducible, 2-fold higher average specific activity. Given the level of incorporation and the distribution of species, the species of modified enzyme responsible for this increase in specific activity is most likely even faster. Further, moving the fluorine atom from the meta- to the para-position of Phe results in a 4-fold decrease in specific activity and a decrease in conformational stability of 1.5 kcal/mol. Since none of the Phe residues in PvuII endonuclease lies near the DNA recognition or catalytic sites, this differential behavior alludes to the impact of subtle changes in enzyme conformation on endonuclease activity and suggests novel ways to influence catalytic behavior.

Allosteric Site↗

PubMed2001

Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer.

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)-based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU-based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P =.036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P =.17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU-based chemoradiation.

Adult↗

PubMed2001

The PD...(D/E)XK motif in restriction enzymes: a link between function and conformation.

The active sites of Mg(II)-dependent nucleases feature a cluster of conserved charged residues which includes both acidic (Asp and Glu) and basic (Lys) side chains. In restriction enzymes, these side chains are part of the conserved PD...(D/E)XK functional sequence motif which has been implicated as being important in metal ion binding and catalytic steps. Recent work revealing the unusual behavior of the active site variant D58A of the representative PvuII endonuclease prompted speculation that the array of charged groups in the nuclease active site may also be linked to conformational behavior [Dupureur, C. M., and Conlan, L. H. (2000) Biochemistry 39, 10921-10927]. To address this issue, we analyzed the conformational behavior of active site variants of PvuII endonuclease using both NMR spectroscopic and thermodynamic methods. NMR spectroscopic analysis via (19)F and (1)H-(15)N HSQC experiments indicates that a number of side chain and backbone amide groups are perturbed upon Ala substitution at conserved active site residues Asp58, Glu68, and Lys70. Spectral changes are particularly pronounced for the lowest-activity mutants (D58A and K70A). These changes are accompanied by perturbations in conformational stability. Ala substitution at each of these positions results in 2-5 kcal/mol of stabilization over the wild-type enzyme at pH 7.7, changes which constitute increases in DeltaG(d)(H2O) of 20-50%. The pH dependencies of mutant enzyme stabilities are distinct from those of the wild type, results which confirm that these ionizable groups strongly influence stability. Wild-type enzyme stability is correlated with the ionization of groups shown to be important to metal ion binding and orientation. Correlations between spectral changes and conformational stability indicate that the latter measurements may prove useful in the evaluation of site-directed mutant restriction enzymes. More importantly, these results indicate that structure-function relationships in restriction enzyme active sites can be complex, and that the ensemble of conserved charged residues which mediate DNA hydrolysis in Mg(II)-dependent nucleases constitutes a critical link between function and conformation.

Alanine↗

PubMed2000

Hyperfractionated radiotherapy concomitant with cisplatin and granulocyte colony-stimulating factor (filgrastim) for laryngeal carcinoma.

An open-label, non-randomized study evaluated the feasibility and efficacy of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor, r-metHuG-CSF) to prevent mucositis induced by accelerated hyperfractionated radiotherapy (1.6 Gy b.i.d., total dose 67.2 Gy in six weeks with a two-week split) and concomitant chemotherapy (cisplatin, 20 mg/m2/day, days 1-5 by continuous intravenous infusion) in patients with laryngeal carcinoma. Filgrastim 300 microg/day was administered on days 1, 3, and 5 in weeks 2-6 of radiotherapy, after the second fraction. Twenty patients (three stage II, six stage III, and eleven stage IV, according to AJCC) were enrolled in the trial. Oral mucosal toxicity was grade 2 in nine patients (45%), grade 3 in eight (40%), and grade 4 in three (15%). Severe hematological toxicity (WHO criteria) was uncommon. Nineteen patients (95%) completed the treatment in the planned time. Overall survival was 55% at three years. The administration of filgrastim with this regimen was feasible, and it appeared to reduce the severity and duration of mucositis induced by the combined treatment.

Adult↗

PubMed1998

Antibiotic resistance in respiratory pathogens.

Antibiotic resistance in respiratory pathogens has dramatically increased during recent years. Resistance to penicillin and multiple antimicrobial agents in pneumococci and resistance to ampicillin in Moraxella catarrhalis and Haemophilus influenzae, as a result of betalactamase production, have become highly prevalent worldwide. The emergence of multiple drug-resistant tuberculosis in different countries is of concern, and has become a therapeutic challenge.

Journal Article↗

PubMed1998

Antibiotic resistance in respiratory pathogens.

Drug Resistance, Microbial↗

PubMed1996

Nosocomial Staphylococcus aureus bacteremia among nasal carriers of methicillin-resistant and methicillin-susceptible strains.

OBJECTIVES: To determine the relevance of nasal carriage of Staphylococcus aureus, either methicillin-sensitive (MSSA) or methicillin-resistant (MRSA), as a risk factor for the development of nosocomial S aureus bacteremia during an MRSA outbreak. PATIENTS AND METHODS: In this prospective cohort study, 488 patients admitted to an intensive care unit (ICU) during a 1-year period were screened with nasal swabs within 48 hours of admission and weekly thereafter in order to identify nasal S aureus carriage. Nasal staphylococcal carriers were observed until development of S aureus bacteremia, ICU discharge, or death. RESULTS: One hundred forty-seven (30.1%) of 488 patients were nasal S aureus carriers; 84 patients (17.2%) harbored methicillin-sensitive S aureus; and 63 patients (12.9%) methicillin-resistant S aureus. Nosocomial S aureus bacteremia was diagnosed in 38 (7.7%) of 488 patients. Rates of bacteremia were 24 (38%) of the MRSA carriers, eight (9.5%) of the MSSA carriers, and six (1.7%) of noncarriers. After adjusting for other predictors of bacteremia by means of a Cox proportional hazard regression model, the relative risk for S aureus bacteremia was 3.9 (95% confidence interval, 1.6-9.8; P = 0.002) for MRSA carriers compared with MSSA carriers. CONCLUSIONS: Among ICU patients, nasal carriers of S aureus are at higher risk for S aureus bacteremia than are noncarriers; in the setting of an MRSA outbreak, colonization by methicillin-resistant strains represents a greater risk than does colonization by MSSA and strongly predicts the occurrence of MRSA bacteremia.

Adult↗

PubMed1996

Molecular tracking of coagulase-negative staphylococcal isolates from catheter-related infections.

Three molecular typing methods (pulsed-field electrophoresis, localization of the mecA gene, and probing the vicinity of mec) have been used for the characterization of 40 catheter-related isolates of coagulase-negative staphylococci (CNS) in 14 patients admitted to the same hospital. The 40 isolates yielded 14 different SmaI banding patterns and corresponding unique localizations of mecA, each associated with a unique ClaI mecA polymorph. In 6 of the 14 patients the contaminated skin at the catheter entry site was the source of 4 local infections and 2 cases of bacteremia. A contaminated hub was the origin of 2 local infections and 4 cases of bacteremia in 6 more patients. The remaining 2 patients had positive cultures from both skin and catheter hub. In each bacteremic patient, the CNS recovered from catheter-related sites (tip, skin, and/or hub) and the CNS recovered from blood were identical, but each of these matching isolates was unique to the particular patients, indicating a low rate of cross-infection from patient to patient. Although classical methods for typing CNS (e.g., biotype and antibiotype) are readily available for most hospital laboratories, they have limitations concerning reproducibility and discriminatory power. Molecular epidemiologic techniques can provide powerful support to traditional techniques in determining the etiologic role of CNS in the disease process.

Bacterial Proteins↗

PubMed1996

Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis.

We studied 122 stool samples collected from 25 patients with hematologic malignancies who received prophylactic norfloxacin. Fecal samples were obtained at admission and twice weekly thereafter during prophylaxis. Fluoroquinolone-resistant Escherichia coli strains were isolated from the feces of 10 (40%) of the patients; two patients had fluoroquinolone-resistant E. coli strains prior to beginning norfloxacin treatment, and in the other eight patients, the strains appeared subsequently. One patient developed fluoroquinolone-resistant E. coli bacteremia after 10 days of norfloxacin administration.

Acute Disease↗

PubMed1994

Spread and maintenance of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone during an outbreak of MRSA disease in a Spanish hospital.

It was not until November 1989 that the 1,000-bed University-affiliated Hospital de Bellvitge "Princeps d'Espanya" in Barcelona first acquired methicillin-resistant Staphylococcus aureus (MRSA). Since that time, the outbreak of MRSA disease has continued. We have analyzed by genomic DNA fingerprinting 189 MRSA isolates collected between late 1989 and the end of 1993. The isolates include both invasive and colonizing strains as well as isolates from health-care workers and environmental sources. In addition, 52 clinical isolates of methicillin-susceptible S. aureus (MSSA) collected in the same hospital were also analyzed. Isolates were classified into clonal types on the basis of molecular typing techniques. A single MRSA clone (I::B::a) belonging to ClaI type I, pulsed-field gel electrophoretic pattern B, and Tn554 pattern a was responsible for the great majority of infections (73% of blood cultures and 79% of specimens from other clinical sources). This clone appeared at the very beginning of the outbreak, spread throughout the hospital wards, and was also carried by inpatients and health-care workers and on environmental surfaces. In contrast, no dominant lineage was apparent among MSSA isolates (33 distinct pulsed-field gel electrophoretic patterns among 52 isolates). Two MSSA isolates seem to have originated from the dominant clone by deletion of the mecA gene and some additional DNA. In several isolates, different mecA polymorphs were present in identical chromosomal backgrounds or cells with distinct chromosomal backgrounds carried the same mecA polymorph, suggesting horizontal transfer of the mecA gene.

Adult↗

PubMed1993

Neoadjuvant chemotherapy and radiotherapy in locally advanced esophagus carcinoma: long-term results.

PURPOSE: A prospective study with neoadjuvant chemotherapy and radiotherapy in patients with locally advanced esophagus carcinoma for evaluating: toxicity, response rate, pattern of recurrence, and survival after a long follow-up. METHODS AND MATERIALS: Between 1983-1988, 40 patients with locally advanced squamous cell carcinoma of the thoracic esophagus were entered into a prospective trial of neoadjuvant chemotherapy and radiotherapy. Eight patients (20%) were Stage II and 32 patients (80%) were Stage III, according to American Joint Committee staging criteria. Neoadjuvant chemotherapy consisted of two cycles with cisplatin (120 mg/m2 day 1), vindesine (3 mg/m2 days 1, 8, 15, and 22) and bleomycin (10 mg/m2 days 3 to 6). Second cycle was initiated on day 29. Radiation therapy was administered 2-4 weeks after completion of chemotherapy, with a total dose on tumor of 60 Gy. RESULTS: Two patients died from treatment-related toxicity. Complete response was observed in 20 patients (53%) and symptomatic improvement in 31 patients (82%). The median survival was 11 months, with an actuarial survival at 1 year of 45%, 3 year 20%, and 5 years 15%. Significantly (p < 0.05) longer survival was observed in patients with Stage II (median survival 18 months) vs. Stage III (median survival 10 months). The pattern of failure was predominantly local/regional (62%). CONCLUSION: This treatment scheme is an effective and tolerable regimen but long-term survival was poor.

Adult↗

PubMed1993

Selective bowel decontamination, nutritional therapy and bacterial translocation after burn injury.

We studied the influence of selective bowel decontamination (SBD) with neomycin, on bacterial translocation (BT) in rats treated with early post-burn parenteral nutrition (TPN) or enteral nutrition (TEN). Male Wistar rats were randomly assigned to receive either TPN (groups 1, 2) or an isonitrogenous, isocaloric polymeric diet (TEN, groups 3, 4) or a standard rat chow ad libitum (group 5), for 5 days after burn injury (30% b. s. area). In addition, groups 1 and 3 received a daily oral dose of neomycin (30 mg/kg) during the same period. At the end of the study, animals were killed and the mesenteric lymph nodes (MLN), liver (L) and spleen (S) were removed for microbiological cultures. The overall incidence of BT was MLN: 67%, L: 58% and S: 42% with a mortality rate of 12.2% In MLN and L, group 5 showed significantly less BT than groups 1 and 2 (30% vs 84%, p < 0.02) and groups 3 and 4 (38% vs 76%, p < 0.05), respectively. No differences were found between TPN and TEN groups. SBD (groups 1 and 3) resulted in a significantly lower mortality rate (26% vs 0%, p < 0.05) and BT in the liver (38% vs 100%, p < 0.001) than rats without antibiotic treatment (groups 2 and 4). It is concluded that early post-injury TPN or TEN promote BT to a greater extent than a standard chow. In addition, SBD with neomycin prevents mortality and BT after burn injury.

Journal Article↗

PubMed1979

[Not Available].

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Argentina↗

PubMedDate not supplied

T helper and T suppressor subpopulations in pollinosis. Effect of specific immunotherapy.

In this work, possible alterations in OKT-4+ and OKT-8+ cells in relation to pollinosis in studied, 33 pollinic patients were studied. 11 of these had not received immunotherapy and the rest had been treated with specific immunotherapy. The possible effect of immunotherapy on the T helper/T suppressor ratio is evaluated. No significant differences between the two groups of patients were found neither in relation to duration of immunotherapy nor in relation to the control group.

Desensitization, Immunologic↗