European journal of pediatrics
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The fundamental abnormality in asthma is inflammation of the airways. T-helper 2 (Th2) lymphocytes are the key orchestrators of this inflammation, initiating and propagating inflammation through the release of Th2 cytokines. Interleukins(IL)-4, IL-5 and IL-13. IL-4 and IL-13 promote IgE production by B-cells, mast cell growth and differentiation, and upregulate adhesion molecule expression on vascular endothelium. IL-4 also promotes differentiation of uncommitted Th0 lymphocytes into Th2 lymphocytes. IL-5 promotes differentiation and recruitment of eosinophils and activates them to degranulate within tissues, resulting in damage to the respiratory epithelium. Current treatment of childhood asthma relies predominantly on corticosteroids that have nonspecific anti-inflammatory activity and are associated with potential side-effects. Novel therapies that selectively target the underlying immunopathogenesis hold great promise. Disruption of the Th2 lymphocyte induced allergic inflammatory response represents a novel approach to selectively inhibiting allergic inflammation at its origin. Possible therapeutic interventions include inhibition of Th2 response (CpG oligonucleotides, vaccination, CTLA4Ig fusion protein, IL-12, IL-10), inhibition of IgE (the anti-IgE antibody rhuMAb-E25 omalizumab, which is undergoing clinical trials), inhibition of mediator activity (leukotriene modifiers, which are approved for use in childhood asthma), and targeting Th2 cytokines (soluble IL-4 receptors, IL-5 antibody, IL-13). Other therapeutic approaches targeting downstream events in the allergic inflammatory cascade are also currently under investigation (chemokine receptors CCR3, tryptase inhibitors, and inhibitors of cyclic AMP-specific phosphodiesterase 4). ⋯ As we further understand the pathophysiology of asthma, the potential to develop novel treatments increases. This paper addresses current possible new treatments for the future.
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Review Case Reports
Multiple herpetic whitlow lesions in a 4-year-old girl: case report and review of the literature.
Herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles. In children it typically occurs after auto-inoculation from herpes stomatitis, herpes labialis or genitalis. Occasionally, person-to-person transmission occurs from family members with herpes labialis. We report a 4-year-old girl with multiple herpetic whitlows secondary to herpetic stomatitis and present a review of the medical literature based on a systematic MEDLINE search of published paediatric patients (English, French and German language). Of 42 identified patients, 72% were younger than 2 years, most had endogenous or exogenous inoculation of herpes simplex virus type 1 and 65% were initially misdiagnosed as having "bacterial felon". Recurrences were reported in 23%. ⋯ herpetic whitlow should be suspected based on clinical signs. Specific diagnosis can be made by polymerase chain reaction or culture. The high rate of misdiagnosed cases indicates that this entity is not sufficiently known. Lesions are self-limited; surgical interventions can be harmful and should be avoided. Recurrences occur as frequently as in adults.
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The World Health Organisation recommends nasopharyngeal catheters as a safe and efficient method of oxygen administration in infants. However, little is known about the mechanisms of the improvement in oxygenation. The aim of the present study was to determine whether nasopharyngeal oxygen therapy produces positive end-expiratory pressure (PEEP). Nine spontaneously breathing infants (median age 13 months, range 10 days to 20 months) after heart surgery were investigated. All patients had normal pulmonary blood flow at the time of the study (Qp:Qs=1:1). Oxygen (oxygen fraction 1.0) was delivered by an 8 F catheter inserted into the nasopharynx (tip just visible below the soft palate). The pulmonary mechanics were analysed using a single compartment model of the respiratory system. Oesophageal pressure (Pes) at end-expiration, dynamic lung compliance (C(L)) and resistance (R(L)), minute ventilation, PaCO2 and PaO2 were measured at baseline without a nasopharyngeal catheter or oxygen, and at oxygen flows of 0.5 l/min, 1.0 l/min and 2.0 l/min. All the flows generated significant increases in PEEP. Mean difference in PEEP (SD, paired t-test versus baseline): 1.6 cm H2O (1.4, P=0.008) with 0.5 l/min of oxygen; 2.8 cm H2O (2.7, P=0.014) with 1.0 l/min of oxygen; and 4.0 cm H2O (2.9, P = 0.004) with 2.0 l/min of oxygen. There was a significant correlation between all the nasopharyngeal flows (in ml/kg per min) and the generated PEEP (P<0.001) and between the C(L) values and the generated PEEP (P < 0.05). There was no significant difference in PaCO2 and R(L). Minute ventilation was significantly less with nasopharyngeal oxygen than at baseline. As expected, PaO2 increased significantly with increasing oxygen flows. ⋯ Administration of oxygen through an 8 F nasopharyngeal catheter at flow rates recommended by the World Health Organisation (0.5 l/min in newborns, 1.0 l/min in infants) produces moderate amounts of positive end-expiratory pressure. The levels achieved may contribute to an improvement in oxygenation by altering the visco-elastic properties of the lung.
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In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25-34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0-24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487-10000 pg/ml), IL-10 (median 113 pg/ml, range 70-196 pg/ml), CRP (median 22 mg/l, range 4-80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747-8000 pg/ml, IL-10 (median 84 pg/ml, range 76-92 pg/ml), CRP (median 10 mg/l, range 8-33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595-7950 pg/ml), IL-10 (median 80 pg/ml, range 61-147 pg/ml), CRP (median 3 mg/l, range 2.8-8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198-349 pg/ml; IL-10 median 36 pg/ml, range 19-50 pg/ml; CRP median < 2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r = 0.65; P = 0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422-753 pg/ml; CRP median 123 mg/l, range 20-219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61-143 pg/ml; CRP median 8 mg/l range 3-46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538-800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53-161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r = 0.45; P = 0.05). ⋯ Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis.