Increased concentrations of endothelin-1 messenger RNA in tissues and endothelin-1 peptide in plasma in septic pigs: modulation by betamethasone

OBJECTIVES: To study the expression of preproendothelin-1 messenger RNA (mRNA) in tissue after Escherichia coli lipopolysaccharide challenge and to evaluate the possible effects of betamethasone both regarding endothelin-1 production as well as hemodynamic and vascular effects during E. coli lipopolysaccharide infusion in pigs in vivo. DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Ten domestic pigs, weighing 18 to 25 kg. INTERVENTIONS: Anesthetized pigs were given continuous infusions of E. coli lipopolysaccharide (15 micrograms/kg/hr for 3 hrs), with or without prior treatment with betamethasone (0.5 mg/kg im 12 hrs before the start of the surgical preparation and 0.5/kg iv at the start of the preparation). MEASUREMENTS AND MAIN RESULTS: The E. coli lipopolysaccharide infusion evoked the characteristic cardiovascular changes observed in septic shock: decreased mean arterial pressure and cardiac output; increased heart rate and increased pulmonary vascular resistance. Large increases in both arterial plasma concentrations of endothelin-1-like immunoreactivity, as well as preproendothelin-1 mRNA concentrations in tissues, were also observed during the E. coli lipopolysaccharide infusion. Treatment with betamethasone significantly attenuated the E. coli lipopolysaccharide-induced increase in endothelin-1 plasma concentrations, whereas the increased mRNA concentrations were only slightly affected. Furthermore, betamethasone treatment also affected cardiovascular parameters, with significant attenuation of the E. coli lipopolysaccharide-induced increase in heart rate and a higher cardiac output after 60 mins of the E. coli lipopolysaccharide infusion. The urine production, which was markedly decreased during the E. coli lipopolysaccharide infusion, was significantly higher in the betamethasone-treated group compared with the control group. CONCLUSIONS: The present results indicate that the increased concentrations of endothelin-1-like immunoreactivity that are observed in septic shock may have negative effects on both cardiovascular parameters as well as renal function, which is in agreement with a possible role for endothelin-1 in the pathogenesis of septic shock.     

Evaluation of the completion of influenza vaccination

OBJECTIVE: To find the reasons which determine failures to comply with anti-flu vaccinations, so that these can be corrected and the coverage of this preventive action be increased. DESIGN: Observational crossover study, done by means of a telephone survey of people over 65. A questionnaire with closed questions, composed after a pilot study and validated by Cronbach's alpha. SETTING: Primary Care Centre (PCC). PATIENTS: We calculated a population sample for qualitative variables (_ = 0.05; p = 0.60; e = 0.05) of 294 people over 65, chosen from the PCC records, by means of random sampling (K = 4) stratified for age and discounting the telephone selection bias. MEASUREMENTS AND RESULTS: The proportion of vaccinated patients (60.9%) obtained in our study did not significantly differ from that in the general population. The percentage of patients included in the programme for the first time was 14%. Level of satisfaction among those vaccinated was 89.4%, with 8.9% of problems detected being light. Main causes of non-vaccination were: thinking that they didn't need it (63.5%), ignorance of the campaign (35.7%), fear of the reaction (24.3%), forgetting (10.4%). The main form of access to the campaign information was from the PCC, both through individuals and posters. Lack of information was statistically significant (p < 0.00001) as a determinant of non-vaccination, without other factors (age, sex, associated pathologies...) explaining these differences. CONCLUSIONS: Individualised and on-going health education by the PCC is fundamental. This would enable the identification of the group not vaccinated due to their express refusal and the recovery of non-vaccinated patients.     

The potato mitochondrial initiator methionine tRNA gene and its flanking regions: an illustration of the diversity of mitochondrial genome rearrangements among plant species

The initiator methionine transfer RNA (tRNA(fMet)) gene was identified on a 347 bp Eco RI-Hind III DNA fragment of the potato mitochondrial (mt) genome. The sequence of this gene shows 1 to 7 nucleotide differences with the other plant mt tRNAs(fMet) or tRNA(fMet) genes studied so far. Whereas the tRNA(fMet) gene is present as a single copy in the potato mt genome, a tRNA 'pseudogene' corresponding to 60% of a complete tRNA (from the 5' end to the variable region) and located at 105 nucleotides upstream of the tRNA(fMet) gene on the opposite strand was shown to be repeated at least three times. Furthermore, the physical environment of the tRNA(fMet) gene in the mt genome is very different among plants, which suggests that the tRNA(fMet) gene region has often been implicated in recombination events of plant mt genomes leading to important rearrangements in gene order.     

Study of adenovirus production in serum-free 293SF suspension culture by GFP-expression monitoring

BACKGROUND: Recently, investigators have reported the use of endoscopic myotomy in the treatment of esophageal achalasia. As with the open operation, considerable disagreement exists regarding the appropriate length of the myotomy and the need for a concomitant antireflux procedure. METHODS: Patients presenting with symptomatic achalasia between 1993 and 1997 were included in this prospective study. Preoperative studies included barium upper gastrointestinal study, endoscopy, and esophageal manometry. Laparoscopic myotomy was completed in all 20 patients; 18 had concomitant Toupet fundoplication. RESULTS: Operative times ranged from 95 to 345 minutes (mean 216). Blood loss ranged from 50 to 300 cc (mean 100 cc). There were 7 minor complications (5 mucosal injuries repaired laparoscopically, 1 bile leak and 1 splenic capsular tear). Nine patients began a liquid diet on the first day postoperatively; 19 were tolerating liquids by postoperative day 3. Hospital stay ranged from 2 to 20 days (mean 5). Eighteen patients had complete relief of dysphagia, with less than one reflux episode per month. One individual continues to have mild persistent solid food dysphagia. Another patient initially did well but subsequently developed mild recurrent dysphagia and reflux. One patient required laparoscopic take-down of the wrap because of recurrent dysphagia and now has no problems swallowing, but does complain of mild reflux. Two other patients also have mild reflux, 1 of whom did not undergo fundoplication. CONCLUSIONS: Laparoscopic Heller myotomy can be performed safely with excellent results in patients with achalasia. Adding a partial fundoplication appears to help control postoperative symptoms of reflux. This procedure should be considered the procedure of choice in patients with symptomatic esophageal achalasia.