Early and late onset bacteremia have different risk factors in trauma patients

Objective The aim of this study was to identify risk factors and to describe epidemiological patterns for early—(EOB) and late—onset bacteremias (LOB) after trauma.Design A prospective study conducted on 141 consecutive trauma patients.Setting A general intensive care unit (ICU) of a university hospital.Patients All multiple trauma patients admitted to our general intensive care unit (ICU) from December 1990 to May 1992 were prospectively enrolled in the study. The following information was collected for each patient and recorded in a computer database: demography, severity of trauma according to the Abbreviated Injury Scale (AIS), severtity of trauma according to the Glasgow Coma Scale (GCS), presence of pneumothorax, pulmonary contusion, rib fractures, hemothorax, and abdominal trauma, use of mechanical ventilation, and placement of central venous catheters. Bacteremias were defined as EOB when onset occurred within 96 h after trauma, and as LOB when appearing after 96 h from trauma.Results Thirty-seven patients developed bacteremia during their ICU stay (26%): 11 (29.7%) EOB and 26 (70.3%) LOB. Gram-positive cocci were isolated more frequently in EOB than in LOB (x ²=4.1,P=0.04). The risk of EOB was significantly increased by the presence of pulmonary contusion [relative risk (RR) 15.0; confidence interval (CI) 1.99-113.25], pneumonia before the onset of bacteremia (RR 3.56; CI 1.17-10.69), AIS score greater than 32 and an abdominal injury score greater than 9 (RR 3.11; CI 1.02-9.49), while intravascular catheters and mechanical ventilation did not represent risk factors for EOB. LOB had a very different pattern and their risk was significantly increased by exposure to intravascular catheters (RR 4.96; CI 1.23-19.94) and to mechanical ventilation lasting more than 7 days (RR 3.6; CI 1.6-8.1).Conclusions Scoring with the AIS of the abdominal and thoracic trauma at admission to the ICU appears a useful tool for identifying trauma patients at increased risk of EOB. A rigorous policy of catheter placement and maintenance as a means of reducing late bacteremias in trauma patients is essential.     

The HIV-1 vpr Protein Acts as a Negative Regulator of Apoptosis in a Human Lymphoblastoid T Cell Line: Possible Implications for the Pathogenesis of AIDS

Although apoptosis is considered one of the major mechanisms of CD4⁺ T cell depletion in HIV-infected patients, the virus-infected cells somehow appear to be protected from apoptosis, which generally occurs in bystander cells. Vpr is an auxiliary HIV-1 protein, which, unlike the other regulatory gene products, is present at high copy number in virus particles. We established stable transfectants of CD4⁺ T Jurkat cells constitutively expressing low levels of vpr. These clones exhibited cell cycle characteristics similar to those of control-transfected cells. Treatment of control clones with apoptotic stimuli (i.e., cycloheximide/tumor necrosis factor α (TNF-α), anti-Fas antibody, or serum starvation) resulted in a massive cell death by apoptosis. In contrast, all the vpr-expressing clones showed an impressive protection from apoptosis independently of the inducer. Notably, vpr antisense phosphorothioate oligodeoxynucleotides render vpr-expressing cells as susceptible to apoptosis induced by cycloheximide and TNF-α as the control clones. Moreover, the constitutive expression of HIV-1 vpr resulted in the upregulation of bcl-2, an oncogene endowed with antiapoptotic activities, and in the downmodulation of bax, a proapoptotic factor of the bcl-2 family. Altogether, these results suggest that low levels of the endogenous vpr protein can interfere with the physiological turnover of T lymphocytes at early stages of virus infection, thus facilitating HIV persistence and, subsequently, viral spread. This might explain why apoptosis mostly occurs in bystander uninfected cells in AIDS patients.     

Viable cryopreserved aortic homograft for aortic valve endocarditis and annular abscesses

Six consecutive patients with active aortic valve endocarditis, including 2 with extensive subannular aortic root abscess, were successfully treated with viable cryopreserved homograft aortic valve replacement. Two patients required extensive aortic root reconstruction with an appropriately trimmed aortic homograft to cover large abscess cavities. All patients showed resolution of infection with no perioperative mortality or clinically significant morbidity. Three patients had a minor degree of aortic insufficiency on postoperative echo-Doppler study. On follow-up at 6 to 48 months, all patients were in New York Heart Association functional class I. The resistance of the unstented homograft to infection makes it an attractive choice for patients requiring aortic valve replacement for active endocarditis. The results of surgical intervention in patients with extensive aortic root involvement may be further improved by the flexibility afforded by the homograft to be "custom-fit" to the abnormal aortic root and the ability to achieve secure abnormal aortic root and the ability to achieve secure valve fixation without use of prosthetic material.     

Effect of etoposide (VP16-213) on lipid peroxidation and antioxidant status in a high-dose radiochemotherapy regimen

Summary A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2±60 mg/kg). Patients stratified to be at high risk for relapse (6/13) were additionally treated with etoposide (30 mg/kg). Plasma concentrations of absolute and lipid-standardized antioxidants (-tocopherol and -carotene) decreased following conditioning therapy, presumably as the result of an enhanced breakdown of these antioxidants. Etoposide treatment did not amplify the loss of essential anti-oxidants but significantly increased lipid hydroperoxide concentrations in serum. We suggest that the abnormal generation of lipid hydroperoxides is the result of free radical formation.     

Sputum induction as a research tool for the study of human respiratory mucus

The study objectives were to compare in vitro transportability and physical properties of respiratory mucus, obtained invasively by direct collection (DC) right after endotracheal intubation and non-invasively by sputum induction with 3% hypertonic saline solution inhalation (SI) 24 h before the anesthesia. Twenty-two patients with no pulmonary disease scheduled for elective abdominal surgical procedures were studied. The parameters analyzed and the main results are as follows. (1) Transportability by cilia (MCT), SI was higher than DC (0.94+/-0.25 and 0.62+/-0.25; P<0.001). There was a significant correlation between the two methods and DC could be estimated by: DC=0.21+(0.44 SI) (r=0.44; P<0.001). (2) Transportability by cough (CC), SI was higher than DC (68.23+/-32.1 and 33.58+/-19.04 mm; P=0.002). (3) Contact angle (CA), SI was lower than DC (10+/-3 degrees and 22+/-14 degrees ; P=0.025). (4) Rheological properties (no significant difference obtained between SI and DC). These results indicated that SI changes mucus physical properties and transportability in non-expectorators.     

Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk

Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Risk factors include environmental components and genetic determinants. The complement factor H (CFH) has been the first major susceptibility gene for AMD identified within 1q32. Here, we focused on a second region of interest in 10q26 where a recent meta-analysis revealed strongest evidence for linkage to AMD at a genome-wide significance level. Within an interval of 22 Mb, we have analyzed 93 single nucleotide polymorphisms for allelic association with AMD in two independent case-control cohorts of German origin (AMD(combined) n=1166; controls(combined) n=945). Significant association was found across a 60 kb region of high linkage disequilibrium harboring two genes PLEKHA1 and hypothetical LOC387715. The strongest association (P=10(-34)) centered over a frequent coding polymorphism, Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of AMD. Besides abundant expression in placenta, we demonstrate weak expression of LOC387715 in the human retina. At present, however, there is no functional information on this gene, which appears to have evolved recently within the primate lineage. The joint contribution of the common risk allele at LOC387715, Ala69Ser, and at CFH, Tyr402His, was assessed in our case-control population, which suggests an additive model indicating an independent contribution of the two gene loci to disease risk. Our data show a disease odds ratio of 57.6 (95% CI: 37.2, 89.0) conferred by homozygosity for risk alleles at both CFH and LOC387715 when compared with the baseline non-risk genotype.