A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Gentamicin dosage regimen based on serum creatinine concentration

In order to avoid gentamicin toxicity trough serum concentrations when drug monitoring is not available, a correction factor for serum creatinine was calculated and evaluated. In a first group of 35 patients under aminoglycoside treatment with variable serum creatinine (SCr) values, the regression plot of SCr concentrations versus half-life (T1/2) values was established: log T1/2 = log 2.28 + 1.45 log SCr, r = 0.90, p less than 0.01. A second group of 18 patients was treated with doses of 1.0 mg/kg of gentamicin. Dose intervals equivalent to 3 T1/2 were daily adjusted. The T1/2 was calculated from SCr according to the relationship established for the patients of the first group. All the patients studied maintained trough levels within the therapeutic range.     

An assessment of gene prediction accuracy in large DNA sequences

One of the first useful products from the human genome will be a set of predicted genes. Besides its intrinsic scientific interest, the accuracy and completeness of this data set is of considerable importance for human health and medicine. Though progress has been made on computational gene identification in terms of both methods and accuracy evaluation measures, most of the sequence sets in which the programs are tested are short genomic sequences, and there is concern that these accuracy measures may not extrapolate well to larger, more challenging data sets. Given the absence of experimentally verified large genomic data sets, we constructed a semiartificial test set comprising a number of short single-gene genomic sequences with randomly generated intergenic regions. This test set, which should still present an easier problem than real human genomic sequence, mimics the approximately 200kb long BACs being sequenced. In our experiments with these longer genomic sequences, the accuracy of GENSCAN, one of the most accurate ab initio gene prediction programs, dropped significantly, although its sensitivity remained high. Conversely, the accuracy of similarity-based programs, such as GENEWISE, PROCRUSTES, and BLASTX was not affected significantly by the presence of random intergenic sequence, but depended on the strength of the similarity to the protein homolog. As expected, the accuracy dropped if the models were built using more distant homologs, and we were able to quantitatively estimate this decline. However, the specificities of these techniques are still rather good even when the similarity is weak, which is a desirable characteristic for driving expensive follow-up experiments. Our experiments suggest that though gene prediction will improve with every new protein that is discovered and through improvements in the current set of tools, we still have a long way to go before we can decipher the precise exonic structure of every gene in the human genome using purely computational methodology.     

Does Flavonoid Consumption Improve Exercise Performance? Is It Related to Changes in the Immune System and Inflammatory Biomarkers? A Systematic Review of Clinical Studies since 2005

Flavonoids are attracting increasing attention due to their antioxidant, cardioprotective, and immunomodulatory properties. Nevertheless, little is known about their role in exercise performance in association with immune function. This systematic review firstly aimed to shed light on the ergogenic potential of flavonoids. A search strategy was run using SCOPUS database. The returned studies were screened by prespecified eligibility criteria, including intervention lasting at least one week and performance objectively quantified, among others. Fifty-one studies (54 articles) met the inclusion criteria, involving 1288 human subjects, either physically untrained or trained. Secondly, we aimed to associate these studies with the immune system status. Seventeen of the selected studies (18 articles) assessed changes in the immune system. The overall percentage of studies reporting an improved exercise performance following flavonoid supplementation was 37%, the proportion being 25% when considering quercetin, 28% for flavanol-enriched extracts, and 54% for anthocyanins-enriched extracts. From the studies reporting an enhanced performance, only two, using anthocyanin supplements, focused on the immune system and found certain anti-inflammatory effects of these flavonoids. These results suggest that flavonoids, especially anthocyanins, may exert beneficial effects for athletes’ performances, although further studies are encouraged to establish the optimal dosage and to clarify their impact on immune status.     

Mutational specificity of aflatoxin B1. Comparison of in vivo host-mediated assay with in vitro S9 metabolic activation

An intrasanguineous host-mediated assay was used to determinethe pattern of mutagenesis induced by the carcinogen aflatoxinBl in the lacl gene of Escherichia coli recovered from rat liver.To investigate the influence of different types of metabolicactivation, the mutation spectrum induced by AFB1 activatedin vitro by a commercially prepared S9 microsomal fraction fromAroclor 1254-treated rats was also obtained. A total of 281forward mutations affecting the N-terminal region of the laclgene were characterized by DNA sequencing analysis. AFB1 inducedsimilar type of mutations with similar site specificity whenactivated by the standard S9 fraction or by employing a rathost-mediated assay. These results indicate the ability of thein vitro S9 fraction to mimic the in vivo metabolism, suggestingthat the same active metabolite, presumably AFB1 8, 9-epoxide,is responsible for generating a similar pattern of DNA damage,as reflected in the similarity of mutational spectra. For bothactivation systems, most mutations (>90%) were base substitutionsthat occurred primarily at G: C pairs. Somewhat over one-halfof G: C targeted substitutions were GC>TA transversions,other mutations being evenly divided between G: C>AT transitionsand GC>CG trans-versions. The mutational specificity exhibitedby activated AFB1 can be explained by incorporation of differentbases opposite a single type of non-instructive lesion duringerror-prone DNA synthesis. To what extent the mutations aredue to the main adduct (AFB1-N7-Gua), its imidazole-ring-openedderivative or an apurinic site remains unknown.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

PURPOSE: Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. PATIENTS AND METHODS: Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. RESULTS: By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. CONCLUSION: Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.     

Estudio de intervención formativa con miniensayos para mejorar la atención de las urgencias médicas en un centro de salud

ObjectiveTest effectiveness and acceptability of interventions short essay-type training in health emergency management (EM).DesignCombined case series and controlled study before and after training sessions.LocationHealth Center (HC).ParticipantsTeam on duty, two monitors-facilitators, and a mannequin.Main measuresVariables: response times, staff performance, resource usage and opinion. Structure: scenarios and key messages. Instrument development: 1. Initial/final questionnaire and events. 2. Essential/non-essential times; 3. Post-test opinion questionnaire. Performance of six consecutive 15 min tests fortnightly (including corrections) and poll after each test. A month later, repeat in random order and under similar conditions. Analysis: repeated measures.ResultsA total of 93 (2/3) workers completed the initial survey, and 74 the final, with 46 participants (25 doctors, 7 nurses, 21 non-health completed 95 direct interventions. Matching participants > 80% between series. A reduction was seen in the “detection of collapse to first defibrillation” interval (10 to 4 min). EM events improved 2-3 fold and “sense of security during a real EM” increased from 23% to 71% among participants. The vast majority of participants said “useful corrections made by the facilitator.” The proportions of those who “would like to see tests introduced” and those who said “re-training was needed in EM” were moderately increased (67.4% vs 85% in health care workers). The “would like to attempt basic life support” was unchanged.ConclusionDespite being reduced in number and duration, this model of intervention has shown positive trends in terms of use and acceptability for implementation in the HC.