A redox basis for metronidazole resistance in Helicobacter pylori.

Metronidazole resistance in Helicobacter pylori has been attributed to mutations in rdxA or frxA. Insufficient data correlating RdxA and/or FrxA with the resistant phenotype, and the emergence of resistant strains with no mutations in either rdxA or frxA, indicated that the molecular basis of H. pylori resistance to metronidazole required further characterization. The rdxA and frxA genes of four matched pairs of metronidazole-susceptible and -resistant strains were sequenced. The resistant strains had mutations in either rdxA, frxA, neither gene, or both genes. The reduction rates of five substrates suggested that metabolic differences between susceptible and resistant strains cannot be explained only by mutations in rdxA and/or frxA. A more global approach to understanding the resistance phenotype was taken by employing two-dimensional gel electrophoresis combined with tandem mass spectrometry analyses to identify proteins differentially expressed by the matched pair of strains with no mutations in rdxA or frxA. Proteins involved in the oxireduction of ferredoxin were downregulated in the resistant strain. Other redox enzymes, such as thioredoxin reductase, alkyl hydroperoxide reductase, and superoxide dismutase, showed a pI change in the resistant strain. The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance.

Evaluation of gastric motility through surface electrogastrography in critically ill septic patients. Comparison of metoclopramide and domperidone effects: A pilot randomized clinical trial. / Evaluación de motilidad gástrica mediante electrogastrografía de superficie en pacientes críticos sépticos. Comparación de los efectos de metoclopramida y domperidona: un ensayo clínicopiloto aleatorizado.

INTRODUCTION AND AIMS: Critically ill patients present with a broad spectrum of gastrointestinal motility disorders that affect the digestive tract. Our aim was to compare the effect of two prokinetic drugs on gastric electrical rhythm in critically ill septic patients, measured through surface electrogastrography (EGG). MATERIAL AND METHODS: A prospective triple-blinded randomized study was conducted on 36 patients admitted to the intensive care unit (ICU) with the diagnosis of septic shock. They were randomized to receive metoclopramide or domperidone. We assessed dominant frequency (DF), percentage distribution over time, and dominant power (DP), which represents the strength of contraction, before and after administration of the study drugs. RESULTS: Reliable electrogastrograms were achieved in all patients. In relation to the distribution of DF over time, 64% of patients had dysrhythmia, the mean baseline DF was 2.9 cpm, and the mean DP was 56.5µv After drug administration, 58% of the patients had dysrhythmia, the mean DF increased to 5.7 cpm (P<.05), and the DP did not change (57.4µv2). There were no significant differences between drugs. In the metoclopramide group, the baseline DF was 2.1 cpm and the baseline DP was 26.1µv2. The post-drug values increased to 5.4 cpm and 34.1µv2, respectively. In the domperidone group, the baseline DF was 3.7 cpm and the baseline DP was 86.9µv2. After drug administration, the DF increased to 6.1 cpm and the DP decreased to 83.5µv2. CONCLUSIONS: Both metoclopramide and domperidone similarly increased the DF of gastric pacemaker activity and improved gastric motility by restoring a normogastric pattern. Gastric dysmotility is frequent in septic patients.

Association between entero-hepatic Helicobacter species and Crohn's disease: a prospective cross-sectional study.

BACKGROUND: The pathogenesis of Crohn's disease (CD) involved microbial factors. Some Helicobacter species, the so-called entero-hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans. Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies. METHODS: Two groups of patients were included prospectively in a multicentre cross-sectional study: CD patients with an endoscopic post-operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis. RESULTS: In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age-adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04-6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis. CONCLUSION: Crohn's disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.

Traumatismo materno grave y cirugía múltiple con resultado perinatal exitoso / Multiple surgery in severe maternal trauma with successful perinatal outcome

El traumatismo mayor de la embarazada es frecuente, tiene riesgo de muerte y agrega a sus complicaciones propias, las generadas por el embarazo como prematurez, desprendimiento placentario y daño perinatal. Presentamos el caso de una embarazada de 27 semanas, con traumatismo grave por atropello, fracturas óseas y desforramiento extenso de extremidad inferior derecha, que fue sometida a tratamiento quirúrgico con reducción y corrección de luxofracturas, aseo e injertos cutáneos. Se complica con infección grave de foco cutáneo, persistente, permaneciendo 24 días en Unidad de Cuidad Intensivo (UCI) en tratamiento antibiótico, 10 drenajes quirúrgicos, nutrición enteral y manejo continuo del dolor, antes del parto. Inicia síndrome de respuesta inflamatoria sistémica y se efectúa operación cesárea. El recién nacido prematuro pesó 1500 gramos y evolucionó favorablemente. En su puerperio permanece 60 días hospitalizada en UCI con 14 cirugías de reparación y mejoría completa. Se analiza las características singulares de morbilidad materna del caso, discutiendo los aspectos obstétricos, quirúrgicos y de cuidado intensivo, la evolución materna, el manejo de la infección y el rol de la cirugía en la prolongación del embarazo y su influencia en el resultado perinatal exitoso. Se concluye la importancia de la integración multidisciplinaria en la toma de decisiones médicas y quirúrgicas en el manejo del trauma materno grave.

Maternal trauma is a leading cause of morbidity and mortality for both, fetus and mother. In addition, trauma can generate risks as premature delivery, abruptio placentae and fetal damage. A pregnant women, at 27 gestational weeks had a car accident with dislocation and fractures and extensive skinning of right leg. The first surgery for fracture-dislocations, cleaning and muscle skin flap were complicated with infection from cutaneous focus, serious and persistent. She remainded for 24 days in Intensive Care Unit (ICU) with antibiotic therapy; she had 10 procedures of surgical drainage with anesthesia, catheter enteral nutrition and continuous pain medication before delivery. Then, she presented systemic inflammatory syndrome maternal and a cesarean section was done; the newborn weighted 1500 grams and had a favorable evolution. After delivery the mother stayed 60 days in ICU, with 14 reparatives surgeries and complete recovery. In this special patient with severe maternal morbidity we discuss the etiology of the oligoamnios observed, the maternal evolution in ICU, the handling of infection, the significance of surgical treatment in prolonging pregnancy and its influence on a successful perinatal outcome. We emphasize on the importance of a multidisciplinary approach in making the medical and surgical decisions in severe maternal trauma.