Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: importance in ARDS in septic pediatric critically ill patients.

Accumulating evidence indicates that genetic background influences the outcome of sepsis, which despite medical advances continues to be a major cause of morbidity and mortality. This study aimed to evaluate the influence of SNPs LTA +252A>G, TNF-863C>A and TNF-308G>A on susceptibility to sepsis, acute respiratory distress syndrome (ARDS), septic shock and sepsis mortality. A prospective case-control study was carried out in a Brazilian pediatric intensive care unit and included 490 septic pediatric patients submitted to mechanical ventilation and 610 healthy children. No SNP association was found with respect to sepsis susceptibility. Nevertheless, a haplotype was identified that was protective against sepsis (+252A/-863A/-308G; OR=0.65; p=0.03). We further observed protection against ARDS in TNF-308 GA genotype carriers (OR=0.29; p=0.0006) and -308A allele carriers (OR=0.40; p=0.003). In addition, increased risk for ARDS was detectable with the TNF-863 CA genotype (OR=1.83; p=0.01) and the -863A carrier status (OR=1.82; p=0.01). After stratification according to age, this outcome remained significantly associated with the -308GA genotype in infants. Finally, protection against sepsis-associated mortality was found for the TNF-308 GA genotype (OR=0.22; p=0.04). Overall, our findings document a protective effect of the TNF-308 GA genotype for the ARDS and sepsis mortality outcomes, further providing evidence for an increased risk of ARDS associated with the TNF-863 CA genotype. Trial registration (www.clinicaltrials.gov): NCT00792883.

Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition.

Because low tumor necrosis factor-alpha (TNF-alpha) production has been reported in malnourished children, in contrast with high production of TNF-alpha in experimental protein-energy malnutrition, we reevaluated the production of TNF-alpha in whole blood cultures from children with primary malnutrition free from infection, and in healthy sex- and age-matched controls. Mononuclear cells in blood diluted 1:5 in endotoxin-free medium released TNF-alpha for 24 h. Spontaneously released TNF-alpha levels (mean +/- SEM), as measured by enzyme immunoassay in the supernatants of unstimulated 24-h cultures, were 10,941 +/- 2,591 pg/ml in children with malnutrition (N = 11) and 533 +/- 267 pg/ml in controls (N = 18) (P < 0.0001). TNF-alpha production was increased by stimulation with lipopolysaccharide (LPS), with maximal production of 67,341 +/- 16,580 pg/ml TNF-alpha in malnourished children and 25,198 +/- 2,493 pg/ml in controls (P = 0.002). In control subjects, LPS dose-dependently induced TNF-alpha production, with maximal responses obtained at 2000 ng/ml. In contrast, malnourished patients produced significantly more TNF-alpha with 0.02-200 ng/ml LPS, responded maximally at a 10-fold lower LPS concentration (200 ng/ml), and presented high-dose inhibition at 2000 ng/ml. TNF-alpha production a) was significantly influenced by LPS concentration in control subjects, but not in malnourished children, who responded strongly to very low LPS concentrations, and b) presented a significant, negative correlation (r = -0.703, P = 0.023) between spontaneous release and the LPS concentration that elicited maximal responses in malnourished patients. These findings indicate that malnourished children are not deficient in TNF-alpha production, and suggest that their cells are primed for increased TNF-alpha production.

Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition

Because low tumor necrosis factor-alpha (TNF-alpha) production has been reported in malnourished children, in contrast with high production of TNF-alpha in experimental protein-energy malnutrition, we reevaluated the production of TNF-alpha in whole blood cultures from children with primary malnutrition free from infection, and in healthy sex- and age-matched controls. Mononuclear cells in blood diluted 1:5 in endotoxin-free medium released TNF-alpha for 24 h. Spontaneously released TNF-alpha levels (mean ± SEM), as measured by enzyme immunoassay in the supernatants of unstimulated 24-h cultures, were 10,941 ± 2,591 pg/ml in children with malnutrition (N = 11) and 533 ± 267 pg/ml in controls (N = 18) (P < 0.0001). TNF-alpha production was increased by stimulation with lipopolysaccharide (LPS), with maximal production of 67,341 ± 16,580 pg/ml TNF-alpha in malnourished children and 25,198 ± 2,493 pg/ml in controls (P = 0.002). In control subjects, LPS dose-dependently induced TNF-alpha production, with maximal responses obtained at 2000 ng/ml. In contrast, malnourished patients produced significantly more TNF-alpha with 0.02-200 ng/ml LPS, responded maximally at a 10-fold lower LPS concentration (200 ng/ml), and presented high-dose inhibition at 2000 ng/ml. TNF-alpha production a) was significantly influenced by LPS concentration in control subjects, but not in malnourished children, who responded strongly to very low LPS concentrations, and b) presented a significant, negative correlation (r = -0.703, P = 0.023) between spontaneous release and the LPS concentration that elicited maximal responses in malnourished patients. These findings indicate that malnourished children are not deficient in TNF-alpha production, and suggest that their cells are primed for increased TNF-alpha production.

[Cat-scratch disease caused by Bartonella quintana in an infant: an unusual presentation]. / Doença da arranhadura do gato por Bartonella quintana em lactente: uma apresentação incomum.

This case study reports a typical clinical course of cat-scratch disease (CSD) in an infant without epidemiological data and presenting bilateral submandibular lymphadenopathy. The authors describe clinical course, ultrasound images, diagnosis and prognosis. Polymerase chain reaction (PCR) detected and identified B. quintana in lymph node samples. B. henselae currently thought to be the causative agent of CSD was not detected. The PCR assays for B. quintana and B. henselae should be available for the investigation of lymphadenopathy, even if the infant has not had either cat or dog contact.

[Children with acute respiratory distress syndrome: anatomoclinical and radiologic correlation]. / Estudo de crianças com síndrome do desconforto respiratório agudo: correlação anatomoclínica radiológica.

This retrospective study reviews cases of ARDS (Adult Respiratory Distress Syndrome) treated and followed up from October 1988 to December 1990 in the Pediatric Intensive Care Unit of Instituto Fernandes Figueira/FIOCRUZ, Brazil. Clinical, radiological and histopathological features were analyzed and correlated with well defined stages of the disease process. Out of 459 cases, 49 (11%) were selected for further study. In 11 cases, histopathological examination (4 biopsies and 8 autopsies) was performed and then classified into one of the following phases: exsudative, cellular proliferative and late fibrotic. The work emphasizes the need for further clinical and experimental studies in order to define the mechanisms and the impact of this Syndrome in the pediatric population.