Relative concentrations of endotoxin binding proteins in body fluids in children during pyogenic infection

The serum protein lipopolysaccharide-binding protein [LBP] binds to the lipid A component of bacterial endotoxin and facilitates its delivery to the CD 14 antigen on the macrophages, where proinflammatory cytokines are released and a cascade of host mediators is initiated. The neutrophil granular protein bactericidal/ permeability-increasing progein [B P1] competes with LBP for endotoxin binding and functions as a molecular antagonist of LBP-endotoxin interactions. We have measured concentrations of BPI and LBP in abscess cavities, enclosed infected body fluids, and non-infected body fluids from 36 children whose age ranged between 2 to 12 years [21 males and 15 females]. The mean values +/- SD of BPI/LBP in different body fluids were 12.12 +/- 5.11 in abscess cavities, 0.778 +/- 0.104 in infected body fluids, and 0.022 +/- 0.0624 in non-infected body fluids. The differences in BPI/LBP ratio between the three types of body fluids were highly significant [P < 0.0001]. The mean BPI concentrations was higher in the 8 abscess cavities that contained gram negative organisms than in the 8 with gram positive or no organisms [P<0.005]. BPI concentrations were directly correlated with the quantity of neutrophils within abscess fluids [rs = 0.844, P<0.001] and in infected body fluids [rs = 0.484, P<0.05]. In conclusion, BPI is available in sufficient quantities within abscess cavities for effective competition with LBP for endotoxin. BPI may attenuate the local inflammatory response and the systemic toxicity of endotoxin release during gram-negative infections

Rapid diagnosis of active pulmonary tuberculosis in children by amplicor mycobacterium tuberculosis PCR test

Conventional diagnosis of Mycobacterium tuberculosis by culture generally takes 3 to 8 weeks. Acid fast smears lack sensitivity and can not distinguish M. tuberculosis from other mycobacteria. Rapid differentiation of M. tuberculosis from other mycobacteria species is therefore of great potential benefit. The PCR can provide a rapid and specific identification of M. tuberculosis complex organisms. The reliability of the Roche AMPLICOR Mycobacterium tuberculosis test [AMPLICOR MTB] for the diagnosis of active pulmonary tuberculosis in children was evaluated by testing 204 specimens [sputum, early morning gastric aspirates, and tracheobronchial lavage] which employs a fast and simplified sample preparation method appropriate for routine diagnostic testing. The specimens were taken from 86 children who were suspected of having active pulmonary MTB on the basis of the presence of one or more of the following criteria: [1] positive tuberculin skin test, [2] abnormal chest radiograph consistent with tuberculosis and/or [3] history of exposure to an adult with infectious tuberculosis. In order to evaluate the accuracy of the PCR assay, PCR results were compared with culture, staining techniques and medical history. Of these 204 specimens, 35 were culture positive for M. tuberculosis from 24 patients. 27 specimens were smear positive for acid fast bacteria [AFB]. On initial testing, the sensitivity and specificity of the AMPLICOR MTB assay, compared with culture, were 88.6% and 98.2% respectively. After resolution of discrepancies [by review of medical history], the sensitivity, specificity, and positive and negative predictive values of the AMPLICOR MTB assay were 89.2%, 99.4%, 97.1%, and 97.6%, respectively. One specimen was AMPLICOR MTB positive and culture positive for Mycobacterium avium complex. For AFB smear-positive specimens, the sensitivity, specificity, and positive and negative predictive values of AMPLICOR MTB were 96.4%, 100%, 100%, and 50%, respectively. For AFB smear-negative specimens, the sensitivity, specificity, and positive and negative predictive values of AMPLICOR MTB were 66.7%, 99.4%, 85.7% and 97.6%, respectively. Our results support the use of AMPLICOR MTB for rapid diagnosis of tuberculosis in children whose respiratory specimens are AFB smear positive. Further studies are needed to determine the most clinically relevant and cost-effective use of this assay with AFB smear-negative specimens

Relative concentratiions of endotoxin-binding proteins in body fluids in children during infection

The serum protein lipopolysaccharide-binding protein [LBP] binds to the lipid A component of bacterial endotoxin and facilitates its delivery to the CD 14 antigen on the macrophages, where proinflammatory cytokines are released and a cascade of host mediators is initiated. The neutrophil granular protein bactericidal/permeability-increasing protein [BPI] competes with LBP for endotoxin binding and functions as a molecular antagonist of LBP-endotoxin interactions. We have measured concentrations of BPI and LBP in abscess cavities, enclosed infected body fluids, and non-infected body fluids from 36 children whose age ranged between 2 to 12 years [21 males and 15 females]. The mean values +/- SD of BPI/LBP in different body fluids were 12.12 +/- 5.11 in abscess cavities, 0.778 +/- 0.104 in infected body fluids, and 0.022 0.0624 in non-infected body fluids. The differences in BPI/LBP ratio between the three types of body fluids were highly significant [P<0.0001]. The mean BPI concentrations was higher in the 8 abscess cavities that contained gram negative organisms than in the 8 with gram positive or no organisms [P<0.005]. BPI concentrations were directly correlated with the quantity of neutrophils within abscess fluids [r[s] = 0.844, P< 0.001] and in infected body fluids [r[s] = 0.484, P<0.05]. In conclusion, BPI is available in sufficient quantities within abscess cavities for effective competition with LBP for endotoxin. BPI may attenuate the local inflammatory response and the systemic toxicity of endotoxin release during gram-negative infections

C-reactive protein, procalcitonin, and interleukin-6 as markers for the early diagnosis of neonatal sepsis

C-reactive protein [CRP] is the most common marker used for neonatal bacterial sepsis [NBS]. Because of a delay in levels increase, a sequential determination is necessary. Procalcitonin [PCT] and interleukin-6 [IL 6] have been proposed for NBS diagnosis. We measured CRP, PCT, and IL 6 concentrations on admission and after 24 hours in neonates with bacterial sepsis [group A, 20 neonates], probable infection with or without colonization [group B, 20 neonates], and healthy neonates [group C, 20 neonates]. The cutoff values were: CRP >/= 10mg/l; PCT > 3 micro g/ml; and IL 6 > 100 pg/ml. The sensitivity for dosages 1 and 2 were respectively [group A versus group C]: CRP 75% and 80%, PCT 100%, and 95%, IL 6 100%, and 85%. Specificity: CRP 100% and 100%, PCT 90% and 90%, IL 6 95% and 90%. CRP is a useful marker of NBS but PCT and IL 6 have better sensitivities indicating an earlier response. PCT and IL 6 are complementary markers of NBS

Echocardiographic assessment of inhaled nitric oxide in newborn infants with severe hypoxemia

Nitric oxide inhalation can benefit newborn babies with persistent pulmonary hypertension with right to left extrapulmonary shunt [EPS]. We compared the effects of inhaled nitric oxide [NO] on systemic oxygenation and mean pulmonary blood flow velocity [MPBFV] using doppler ultrasound in severely hypoxic newborn infants with or without extrapulmonary shunt. With a median dose of 20 parts per million [ppm], oxygenation index decreased significantly in both groups [EPS, [p < 0.001] and non-EPS [p <0.05]]. The percentage decrease was significantly greater in the EPS group [p<0.001]. MPBFV increased significantly in the EPS group [p<0.001] only. There was significant correlation between the percentage decrease in oxygenation index and the percentage increase in MPBFV after 1 h of inhaled NO in the EPS group only. We conclude that inhaled NO may improve some newborn infants with severe hypoxemia without significant EPS by improving ventilation perfusion matching. Careful Doppler ultrasound could help to predict the likelihood of beneficial effects of inhaled NO. Nitric oxide being more effective in newborn infants with extrapulmonary shunting than those without by increasing pulmonary blood flow

Transcranial doppler ultrasound versus neurologic examination in detection of cerebral infarction in children with sickle cell disease

Cerebral infarctions are a major source of disability in children with sickle cell disease [SCD], leading to serious impairment in cognitive and motor functions. The aim of the present work is to assess the value of transcranial Doppler ultrasonography [TCD] of the middle cerebral artery [MCA] and neurologic examination in detection of cerebral infarction in children with SCD. The present work included 28 children [10 boys, and 18 girls] aged 5 to 13 years, underwent full neurologic examination, non-contrast CT of the brain, and TCD. TCD was evaluated for maximum flow velocity in the right and left MCAs. The sensitivity and specificity of neurologic examination for identification of patients with infarction were 55.6% and 89.5% respectively. Depending on the alteration in the maximum flow velocity of the MCA either <100 cm/sec or > 200 cm/sec, the TCD allowed detection of 7 out of 9 patients with documented CT evidence of cerebral infarction with only one false positive result [77.9% sensitivity and 94.4% specificity]. The combination of neurologic examination and TCD produced 88.9% sensitivity and specificity, for detection of cerebral infarction. We conclude that TCD of the MCA can be used as a screening method for identifying children with SCD at risk for developing strokes. Single vessel examination namely MCA makes the examination more easy, of shorter duration, and more suitable for children with no need for special preparation or sedation. The combination of neurologic examination and TCD is promising as a sensitive screening test in this patient population