Eficacia y seguridad de la analgesia preventiva con gabapentinoides para pacientes sometidos a cirugía artroscópica de hombro: una revisión sistemática y metanálisis.

OBJECTIVE: To assess the efficacy and safety of preemptive analgesia with gabapentinoids for patients undergoing arthroscopic shoulder surgery. MATERIAL AND METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted in PubMed, Cochrane Library and ScienceDirect databases. Randomized Controlled Trials (RCTs) comparing gabapentinoids (gabapentin and pregabalin) with placebo in patients undergoing shoulder arthroscopic surgery were retrieved. The primary endpoint was the visual analogue scale (VAS) score at 24 hours and cumulative morphine consumption at 24 hours. The secondary outcomes were complications of nausea/vomiting, sedation and dizziness. After tests for publication bias and heterogeneity among studies were performed, data were aggregated for random-effects models when necessary. RESULTS: Five clinical studies (gabapentin group n = 4 and pregabalin group n = 1) were ultimately included in the meta-analysis. Gabapentinoids were associated with reduced pain scores at 24 hours. Similarly, gabapentinoids were associated with a reduction in cumulative morphine consumption at 24 hours. Furthermore, gabapentinoids can significantly reduce the occurrence of nausea/vomiting. There were no significant differences in the occurrence of sedation and dizziness. CONCLUSIONS: Preoperative use of gabapentinoids was able to reduce postoperative pain, total morphine consumption, and morphine-related complications following arthroscopic shoulder surgery. Further studies should determine the optimal dose and whether pregabalin is superior to gabapentin in controlling acute pain after shoulder surgery.

OBJETIVO: Evaluar la eficacia y seguridad de la analgesia preventiva con gabapentinoides para pacientes sometidos a cirugía artroscópica del hombro. MATERIAL Y MÉTODOS: Se llevó a cabo una revisión sistemática y metaanálisis conforme a PRISMA en las bases de datos PubMed, Cochrane Library y ScienceDirect. Se recuperaron ensayos controlados aleatorios (RCT) que comparaban los gabapentinoides (gabapentina y pregabalina) con placebo en pacientes sometidos a cirugía artroscópica del hombro. El punto final principal fue la puntuación de la escala analógica visual (VAS) a las 24 horas y el consumo acumulado de morfina a las 24 horas. Los resultados secundarios fueron complicaciones de náuseas/vómitos, sedación y mareos. Después de realizar pruebas de sesgo de publicación y heterogeneidad entre los estudios, se agregaron datos para modelos de efectos aleatorios cuando fue necesario. RESULTADOS: En última instancia, se incluyeron en el metaanálisis cinco estudios clínicos (grupo de gabapentina n = 4 y grupo de pregabalina n = 1). Los gabapentinoides se asociaron con puntuaciones de dolor reducidas a las 24 horas. Del mismo modo, los gabapentinoides se asociaron con una reducción en el consumo acumulado de morfina a las 24 horas. Además, los gabapentinoides pueden reducir significativamente la aparición de náuseas/vómitos. No hubo diferencias significativas en la ocurrencia de sedación y mareos. CONCLUSIONES: El uso preoperatorio de gabapentinoides fue capaz de reducir el dolor postoperatorio, el consumo total de morfina y las complicaciones relacionadas con la morfina después de la cirugía artroscópica del hombro. Otros estudios deben determinar la dosis óptima y si la pregabalina es superior a la gabapentina en el control del dolor agudo después de la cirugía de hombro.

Reaction-diffusion model for pattern formation in E. coli swarming colonies with slime.

A new experimental colonial pattern and pattern transition observed in E. coli MG1655 swarming cells grown on semisolid agar are described. We present a reaction-diffusion model that, taking into account the slime generated by these cells and its influence on the bacterial differentiation and motion, reproduces the pattern and successfully predicts the observed changes when the colonial collective motility is limited. In spite of having small nonhyperflagellated swarming cells, under these experimental conditions E. coli MG1655 can very rapidly colonize a surface, with a low branching rate, thanks to a strong fluid production and a locally incremented density of motile, lubricating cells.

Combined treatment with venlafaxine and tricyclic antidepressants in depressed patients who had partial response to clomipramine or imipramine: initial findings.

BACKGROUND: We report, after 3 years of work, a case series showing our initial results (efficacy, tolerability, and safety) with the addition of venlafaxine immediate release (IR) to either clomipramine or imipramine in depressed patients who had shown only partial response to maximal doses of one of those tricyclic antidepressants (TCAs) and no further improvement after addition of usual augmentation drugs. METHOD: Eleven patients were treated, 10 of them having a recurrent depressive disorder (DSM-IV) and all of them having current major depression (DSM-IV) that in 9 patients was moderate or severe despite intense TCA treatment as well as usual augmentations. Under open and outpatient conditions, we maintained TCA doses, discontinued previous augmentations, and then added venlafaxine IR to a maximum dosage, if necessary, of 150 mg every 12 hours. There was no control group. Response was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), DSM-IV criteria, the Clinical Global Impressions-Severity of Illness scale, and persistence of improvements after 6 months. We measured clinical tolerance (using the UKU Side Effect Rating Scale), blood pressure and heart rate, electrocardiogram (ECG), and blood TCA levels after adding venlafaxine IR. RESULTS: A sustained improvement (> 50% decrease in HAM-D score plus decrease in DSM-IV severity level) appeared in 9 patients, and sustained full remission (DSM-IV criteria plus HAM-D score < 5) in 7. Panic-agoraphobic symptoms improved in the 2 patients suffering from them. There were no dropouts, and tolerability was good. No significant changes in blood pressure and heart rate, ECG, or blood tricyclic levels were found. CONCLUSION: Addition of venlafaxine to clomipramine or imipramine could be an effective and safe augmentation strategy in depressive patients with partial response to maximum-dose monotherapy. A consistent replication of these initial findings is strongly needed.

A237T as a modulating mutation in naturally occurring extended-spectrum TEM-type beta-lactamases.

A TEM-1 beta-lactamase derivative containing the single amino acid substitution A237T slightly increased (from 24 to 32 microg/ml) the cephalothin MIC for Escherichia coli RYC1000 but did not influence the activities of cefotaxime, ceftazidime, and aztreonam (MICs of 0.03, 0.12, and 0.06 microg/ml, respectively). Despite its apparent neutrality, addition of the A237T mutation to the pair of mutations characterizing TEM-10 (R164S and E240K) had a strong effect on substrate preference. Ceftazidime and aztreonam MICs decreased from 128 and 16 microg/ml to 16 and 2 microg/ml, respectively. In contrast, the cefotaxime MIC increased from 0.5 to 4 microg/ml. The acquisition of apparently neutral or even deleterious mutations results in a very effective mechanism of resistance to different beta-lactams that may be simultaneously or subsequently present in the environment. We propose here that the mutation in position 237 is an example of a modulating mutation and that consideration of this type of mutation may be important for understanding the evolution of beta-lactamases.

In vitro plasmid-encoded resistance to quinolones.

The possibility of plasmid-encoded quinolone resistance is explored in two model systems. In the first, increasing amounts of wild-type gyrA allele moderately increased minimum inhibitory concentrations to quinolone antibiotics. In the second model, a mutant gyrA allele encoded by a multicopy plasmid produced a quinolone resistance phenotype upon its expression in a quinolone-susceptible Escherichia coli strain.

H-NS and RpoS regulate emergence of Lac Ara+ mutants of Escherichia coli MCS2.

Two master growth-phase regulatory proteins, H-NS and sigmaS, are involved in the formation of araB-lacZ fusion clones of Escherichia coli MCS2. The stationary-phase sigma factor RpoS is strictly required for the appearance of such mutants, whereas the histone-like protein H-NS represses their emergence. Our results support the idea that genetic changes leading to adaptive mutation in this model system are regulated by physiological signal transduction networks.

Cyclic AMP receptor protein positively controls gyrA transcription and alters DNA topology after nutritional upshift in Escherichia coli.

The expression of a transcriptional gyrA-lacZ gene fusion throughout the Escherichia coli growth cycle and the effect that mutation delta crp39 had on this expression were studied. The data obtained indicate that the expression of gyrA is growth phase dependent and under the positive control of the cyclic AMP receptor protein (CRP). Complementation analysis of gyrA-lacZ expression with wild-type CRP or variant CRP pc (with a T-to-A mutation at position 158) in a CRP-deficient background suggests that this CRP action is mediated by a class I or class II CRP-dependent promoter(s). Our results also indicate that CRP may be involved in the modulation of DNA topology in the transition from the lag period to the exponential phase of growth.

Modulation of DNA topology by flaR, a new gene from Listeria monocytogenes.

We report the identification of a previously unknown Listeria monocytogenes gene, flaR, which modulates DNA topology. Through the analysis of a Tn917 non-motile mutant, LOSC1, in which production of flagellin was abolished, we have identified a bacterial component involved in gene regulation. The transposon had inserted in flaR, an open reading frame of 531 bp, followed by a second open reading frame of 1252 bp in reverse orientation. On the L. monocytogenes physical map, flaR was located in a different region from that of the flaA gene encoding flagellin. Transcriptional analysis showed that the flaR gene product affects the flaA expression and negatively regulates its own expression. When expressed in Escherichia coli, flaR encodes a protein of 18 kDa (FlaR) whose transcription is osmoregulated. In addition, FlaR also influences the expression of reporter genes containing supercoiling-sensitive promoters such as proU or ompC. The data presented here suggest that FlaR is a histone-like bacterial protein which acts at specific sites to influence DNA topology and, therefore, transcription. flaR is the first gene of this class to be described in Gram-positive pathogenic bacteria.