Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial.

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.

A pilot study on ocular safety and efficacy of infliximab as an antifibrotic agent after experimental filtration surgery

Purpose To evaluate the safety and efficacy of infliximab as an antifibrotic agent after experimental glaucoma filtration surgery in rabbits. Methods In a randomized, prospective, masked-observer study, 30 New Zealand Albino rabbits underwent glaucoma filtration surgery. The animals were allocated to receive either intraoperative application of infliximab (group A) or mitomycin C (MMC) at a concentration of 0.2mg/ml (group B) or balanced salt solution (BSS, control)(group C). Different infliximab doses, namely 1.0mg, 2.0mg, 3.0mg, 4.0mg, 5.0mg in 0.1ml were applied. Bleb survival and characteristics were evaluated over a 30day period. The animals were killed on postoperative day 15 and 30. Histology of the operated eyes was performed to evaluate and grade the amount of scarring in each group.Cellular density was evaluated in each case. Results Infliximab did not appear to improve the outcome of filtration surgery in this model of glaucoma filtration surgery.There was a significant decrease in cellular density in the MMC group compared to the control group (p=0.0352). There was neither a significant decrease in cellular density between the infliximab group and the control group nor between the infliximab group and the MMC group. Overall there was no difference in terms of fibrosis between the three different groups. There was slightly less inflammation in the infliximab group, but not significant. Conclusions In this study intraoperative application of infliximab does not appear to be superior to the application of MMC or a control with regard to bleb survival and fibrosis. This study however demonstrates that intraoperative application of MMC significantly reduces the cellular density of the filtration bleb.

Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death.

BACKGROUND: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown. METHODS: Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models. RESULTS: In groups A-C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection. CONCLUSION: In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.

Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity?

Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 middle aged control subjects. The obese subjects were divided into three groups: A (n = 12) normal glucose tolerance, B (n = 13) impaired glucose tolerance, and C (n = 7) diabetics, and were studied before and after a body weight loss ranging from 9.6 to 33.5 kg consecutive to a 4 to 6 months hypocaloric diet. GIT, measured over 3 h and expressed as percentage of the energy content of the load, was significantly reduced in obese groups A and C (6.2 +/- 0.6, and 3.8 +/- 0.7%, respectively) when compared to their age-matched control groups: 8.6 +/- 0.7 (young) and 5.8 +/- 0.3% (middle aged). Obese group B had a GIT of 6.1 +/- 0.6% which was lower than that of the young control group but not different from the middle-aged control group. After weight loss, GIT in the obese was further reduced in groups A and B than before weight loss: ie, 3.4 +/- 0.6 (p less than 0.001), 3.7 +/- 0.5 (p less than 0.01) respectively, whereas in group C, weight loss induced no further diminution in GIT (3.8 +/- 0.6%). These results support the concept of a thermogenic defect after glucose ingestion in obese individuals which is not the consequence of their excess body weight but may be one of the factors favoring the relapse of obesity after weight loss.

Rivascolarizzazione miocardica con arteria radiale: tecniche chirurgiche a confronto e risultati a breve termine [Myocardial revascularization and radial artery: different surgical strategies and short-term results]

BACKGROUND: The radial artery is routinely used as a graft for surgical arterial myocardial revascularization. The proximal radial artery anastomosis site remains unknown. In this study, we analyzed the short-term results and the operative risk determinants after having used four different common techniques for radial artery implantation. METHODS: From January 2000 to December 2004, 571 patients underwent coronary artery bypass grafting with radial arteries. Data were analyzed for the entire population and for subgroups following the proximal radial artery anastomosis site: 140 T-graft with the mammary artery (group A), 316 free-grafts with the proximal anastomosis to the ascending aorta (group B), 55 mammary arteries in situ elongated with the radial artery (group C) and 60 radial arteries elongated with a piece of mammary artery and anastomosed to the ascending aorta (group D). RESULTS: The mean age was 53.8 +/- 7.7 years; 55.5% of patients had a previous myocardial infarction and 73% presented with a satisfactory left ventricular function. A complete arterial myocardial revascularization was achieved in 532 cases (93.2%) and 90.2% of the procedures were performed under cardiopulmonary bypass and cardioplegic arrest. The operative mortality rate was 0.9%, a postoperative myocardial infarction was diagnosed in 19 patients (3.3%), an intra-aortic balloon pump was used in 10 patients (1.7%) and a mechanical circulatory device was implanted in 2 patients. The radial artery harvesting site remained always free from complications. The proximal radial artery anastomosis site was not a determinant of early hospital mortality. Group C showed a higher risk of postoperative myocardial infarction (p = 0.09), together with female gender (p = 0.003), hypertension (p = 0.059) and a longer cardiopulmonary bypass time. CONCLUSIONS: The radial artery and the mammary artery can guarantee multiple arterial revascularization also for patients with contraindications to double mammary artery use. The four most common techniques for proximal radial artery anastomosis are not related to a higher operative risk and they can be used alternatively to reach the best surgical results

Auditory stimulation does not induce implicit memory during anaesthesia

Background and aim of the study: Formation of implicit memory during general anaesthesia is still debated. Perceptual learning is the ability to learn to perceive. In this study, an auditory perceptual learning paradigm, using frequency discrimination, was performed to investigate the implicit memory. It was hypothesized that auditory stimulation would successfully induce perceptual learning. Thus, initial thresholds of the frequency discrimination postoperative task should be lower for the stimulated group (group S) compared to the control group (group C). Material and method: Eighty-seven patients ASA I-III undergoing visceral and orthopaedic surgery during general anaesthesia lasting more than 60 minutes were recruited. The anaesthesia procedure was standardized (BISR monitoring included). Group S received auditory stimulation (2000 pure tones applied for 45 minutes) during the surgery. Twenty-four hours after the operation, both groups performed ten blocks of the frequency discrimination task. Mean of the thresholds for the first three blocks (T1) were compared between groups. Results: Mean age and BIS value of group S and group C are respectively 40 } 11 vs 42 } 11 years (p = 0,49) and 42 } 6 vs 41 } 8 (p = 0.87). T1 is respectively 31 } 33 vs 28 } 34 (p = 0.72) in group S and C. Conclusion: In our study, no implicit memory during general anaesthesia was demonstrated. This may be explained by a modulation of the auditory evoked potentials caused by the anaesthesia, or by an insufficient longer time of repetitive stimulation to induce perceptual learning.

Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance.

Down syndrome (DS) is characterized by extensive phenotypic variability, with most traits occurring in only a fraction of affected individuals. Substantial gene-expression variation is present among unaffected individuals, and this variation has a strong genetic component. Since DS is caused by genomic-dosage imbalance, we hypothesize that gene-expression variation of human chromosome 21 (HSA21) genes in individuals with DS has an impact on the phenotypic variability among affected individuals. We studied gene-expression variation in 14 lymphoblastoid and 17 fibroblast cell lines from individuals with DS and an equal number of controls. Gene expression was assayed using quantitative real-time polymerase chain reaction on 100 and 106 HSA21 genes and 23 and 26 non-HSA21 genes in lymphoblastoid and fibroblast cell lines, respectively. Surprisingly, only 39% and 62% of HSA21 genes in lymphoblastoid and fibroblast cells, respectively, showed a statistically significant difference between DS and normal samples, although the average up-regulation of HSA21 genes was close to the expected 1.5-fold in both cell types. Gene-expression variation in DS and normal samples was evaluated using the Kolmogorov-Smirnov test. According to the degree of overlap in expression levels, we classified all genes into 3 groups: (A) nonoverlapping, (B) partially overlapping, and (C) extensively overlapping expression distributions between normal and DS samples. We hypothesize that, in each cell type, group A genes are the most dosage sensitive and are most likely involved in the constant DS traits, group B genes might be involved in variable DS traits, and group C genes are not dosage sensitive and are least likely to participate in DS pathological phenotypes. This study provides the first extensive data set on HSA21 gene-expression variation in DS and underscores its role in modulating the outcome of gene-dosage imbalance.

Proteomics of methylene blue photo-treated plasma before and after removal of the dye by an absorbent filter.

Methylene blue (MB) and light are used for virus inactivation of plasma for transfusion. However, the presence of MB has been the subject of concern, and efforts have been made to efficiently remove the dye after photo-treatment. For this study, plasma was collected by apheresis from 10 donors (group A), then treated using the MacoPharma THERAFLEX procedure (MB; 1 microM, and light exposure; 180 J/cm(2)) (group B), and finally filtered in order to remove the dye (group C). Proteins were analyzed by two-dimensional electrophoresis, and peptides showing modifications were characterized by mass spectrometry. Clottable and antigenic fibrinogen levels, as well as fibrin polymerization time were measured. Analyses of the gels focused on a region corresponding to pI between 4.5 and 6.5, and M(r) from 7000 to 58 000. In this area, 387 +/- 47 spots matched, and four of these spots presented significant modifications. They corresponded to changes of the gamma-chain of fibrinogen, of transthyretin, and of apolipoprotein A-I, respectively. A decrease of clottable fibrinogen and a prolongation of fibrin polymerization time were observed in groups B and C. Removal of MB by filtration was not responsible for additional protein alterations. The effect of over-treatment of plasma by very high concentrations of MB (50 microM) in association with prolonged light exposure (3 h) was also analyzed, and showed complex alterations of most of the plasma proteins, including fibrinogen gamma-chain, transthyretin, and apolipoprotein A-I. Our data indicates that MB treatment at high concentration and prolonged illumination severely injure plasma proteins. By contrast, at the MB concentration used to inactivate viruses, damages are apparently very restricted.

Telementoring during endovascular treatment of abdominal aortic aneurysms: a prospective study.

PURPOSE: To explore the use of telementoring for distant teaching and training in endovascular aortic aneurysm repair (EVAR). METHODS: According to a prospectively designed study protocol, 48 patients underwent EVAR: the first 12 patients (group A) were treated at a secondary care center by an experienced interventionist, who was training the local team; a further 12 patients (group B) were operated by the local team at their secondary center with telementoring by the experienced operator from an adjacent suite; and the last 24 patients (group C) were operated by the local team with remote telementoring support from the experienced interventionist at a tertiary care center. Telementoring was performed using 3 video sources; images were transmitted using 4 ISDN lines. EVAR was performed using intravascular ultrasound and simultaneous fluoroscopy to obtain road mapping of the abdominal aorta and its branches, as well as for identifying the origins of the renal arteries, assessing the aortic neck, and monitoring the attachment of the stent-graft proximally and distally. RESULTS: Average duration of telementoring was 2.1 hours during the first 12 patients (group B) and 1.2 hours for the remaining 24 patients (group C). There was no difference in procedural duration (127+/-59 minutes in group A, 120+/-4 minutes in group B, and 119+/-39 minutes in group C; p=0.94) or the mean time spent in the ICU (26+/-15 hours in group A, 22+/-2 hours in group B, and 22+/-11 hours for group C; p=0.95). The length of hospital stay (11+/-4 days in group A, 9+/-4 days in group B, and 7+/-1 days in group C; p=0.002) was significantly different only for group C versus A (p=0.002). Only 1 (8.3%) patient (in group A: EVAR performed by the experienced operator) required conversion to open surgery because of iliac artery rupture. This was the only conversion (and the only death) in the entire study group (1/12 in group A versus 0/36 in groups B + C, p=0.31). CONCLUSIONS: Telementoring for EVAR is feasible and shows promising results. It may serve as a model for development of similar projects for teaching other invasive procedures in cardiovascular medicine.

Relationship between sedimentation sign and morphological grade in symptomatic lumbar spinal stenosis.

PURPOSE: We aimed to study the relationship between two morphological parameters recently described on MRI images in relation to lumbar spinal stenosis (LSS): the first is the sedimentation sign (SedS) and the second is the morphological grading of lumbar stenosis. MATERIALS AND METHODS: MRIs from a total of 137 patients were studied. From those, 110 were issued from a prospective database of symptomatic LSS patients, of whom 73 were treated surgically and 37 conservatively based on symptom severity. A third group consisting of 27 subjects complaining of low back pain (LBP) served as control. Severity of stenosis was judged at disc level using the four A to D grade morphological classification. The presence of a SedS was judged at pedicle level, above or below the site of maximal stenosis. RESULTS: A positive SedS was observed in 58, 69 and 76 % of patients demonstrating B, C and D morphology, respectively, but in none with grade A morphology. The SedS was positive in 67 and 35 % of the surgically and conservatively treated patients, respectively, and in 8 % of the LBP group. C and D morphological grades were present in 97 and 35 % of patients in the surgically and conservatively treated group, respectively, and in 18 % of the LBP group. Presence of a positive SedS carried an increased risk of being submitted to surgery in the symptomatic LSS group (OR 3.5). This risk was even higher in the LSS patients demonstrating grade C or D morphology (OR 65). DISCUSSION AND CONCLUSION: One-third of surgically treated LSS patients do not present a SedS. This sign appears to be a lesser predictor of treatment modality in our setting of symptomatic LSS patients compared to the severity of stenosis judged by the morphological grade.