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We present an infant with post-intubation stridor caused by a bridge-like subglottic stenosis. At the age of 6 weeks he suffered from a RSV infection with the need for endotracheal intubation. At week 10 acute respiratory distress required a re-intubation. Flexible endoscopy was suggestive for laryngomalacia. Rigid endoscopy revealed a subglottic laterolateral mucosal bridge resulting in a doubling of the airway lumen. Histopathological examination showed a fibrinoid pseudomembrane. Follow up endoscopy showed a grade 1 posterior subglottic stenosis without respiratory compromise. This is the first case in the literature of an infant with a post-intubation bridge-like fibrinoid pseudomembranous subglottic lesion.

It is now recognized that epithelial cells lining airways and alveoli are capable of releasing various mediators, which have the potential to modulate local inflammatory reactions. The amount of the 16 kDa Clara cell protein (CC16), an inhibitor of phospholipase A2 activity produced by pulmonary epithelial cells, was measured by means of a sensitive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BALF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 after standard cardiopulmonary bypass surgery, a known risk factor for ARDS). The level of CC16 was compared with other markers of inflammation with a wide range of molecular weights: albumin (nephelometry); total protein (spectrophotometry); beta 2-microglobulin (latex immunoassay); cystatin C (latex immunoassay); alpha 1-antitrypsin (immunoradiometry), and lipocortin-1 (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and significantly higher levels of this protein were observed in BALF from patients with acute lung injury. Changes in BALF Clara cell protein levels differed from those of alpha 2-macroglobulin and the natural phospholipase inhibitor lipocortin-1. Alpha 2-macroglobulin levels were not significantly enhanced in patients at risk for ARDS, but were increased in patients with ARDS; whereas, lipocortin 1 levels were not elevated in either group. Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein recovered in BALF. The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived. The data presented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which might have a protective and immunosuppressive role.

Sputum from patients with cystic fibrosis, bronchiectasis, and chronic bronchitis contains neutrophils and neutrophil proteases, which have been implicated in the pathophysiology of mucus hypersecretion in airways. We asked whether interleukin-8 (IL-8), a potent neutrophil chemoattractant, might be involved in recruiting neutrophils into airways of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis. We found significant neutrophil chemotactic activity in sputum obtained from these patients. The IL-8 concentrations that we measured in sputum of patients with cystic fibrosis (7.1 +/- 1.0 x 10(-9) M, mean +/- SE), bronchiectasis (9.6 +/- 2.9 x 10(-9) M), and chronic bronchitis (2.8 +/- 1.0 x 10(-9) M) have been reported to cause significant chemotaxis in vitro and in airways in vivo, whereas concentrations measured in induced sputum from healthy subjects (1.1 +/- 0.3 x 10(-10) M) do not. A monoclonal antibody to IL-8 significantly inhibited the chemotactic activity in patients' sputum by 75–98%, but not in induced sputum from healthy subjects (9%). We conclude that IL-8 is an important chemotactic factor in sputum of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis, and we suggest that IL-8 accounts, at least in part, for neutrophil recruitment into airways of patients with these diseases.

The presence of histamine and tryptase in serum during and after coronary artery bypass grafting may be an indication for the induction of inflammation. One group of patients received no glucocorticoids, a second one received methylprednisolone before extracorporeal circulation. In the steroid group, no effects were seen on the basal levels of histamine and tryptase. In the other group, two peak levels of histamine were observed, one peak 10 minutes after starting extracorporeal circulation and another peak 4 hours post-surgery. In this group, tryptase was only elevated during the period of extracorporeal circulation. There were no differences between both groups in complement activation. It was concluded that during surgery mast cells were activated but, since tryptase levels decreased in the post-operative period, the increase in histamine level can only be explained by activation of basophils.

The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia with a variety of etiologies, consists of diffuse, acute parenchymal lung injury that results in increased permeability and mechanical dysfunction [1]. In recent years, a large body of research has focused on a key role for polymorphonuclear leukocytes (PMN) in the pathogenesis of ARDS. Recently, interest has shifted from formed blood elements to both the alveolar macrophage, the resident phagocyte of the alveolar space, and cytokines. In this hypothesis, ARDS is related to the uncontrolled production and liberation of many substances, including cytokines. Cytokines are low-molecular weight proteins, arbitrarily divided into several classes: interleukins (originally described as messengers between leukocytes), interferons (named after their ability to interfere in the life cycle of viruses), growth factors, colony-stimulating factors and chemokines. However, most cytokines are pleiotropic and have multiple, diverse, biological activities [2], frequently not related to their original name.

Although elevated concentrations of a few cytokines have been shown to be present in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with the acute (adult) respiratory distress syndrome (ARDS), the pathogenesis of ARDS is largely unknown. Leukaemia inhibitory factor (LIF), a growth factor recently recognised as a polyfunctional cytokine integrated in cytokine networks was measured in unconcentrated BALF of patients from different patient groups. LIF was measured in BALF by means of a specific and sensitive ELISA (detection limit 10 pg/ml) in BALF (lavage of 3 x 50 ml in the right middle lobe). LIF was not detected in the BALF of 13 healthy control patients and in only one (34 pg/ml) out of 25 patients at risk for ARDS (after cardiopulmonary bypass surgery) who underwent BAL 4 h after the end of the extracorporeal circulation. High and detectable levels were found in the unconcentrated BALF of 10 out of 12 patients with full-blown ARDS (212 ± 116, mean ± SEM, range 10–985 pg/ml). There was a good correlation between the level of LIF in the BALF and a number of markers of inflammation such as neutrophils/ml, albumin and protein levels. The biological role of LIF in these BALFs is not readily explained by its currently known actions and it is unknown whether LIF contributes to or is a response to local tissue damage. Our results indicate that this cytokine is part of the inflammatory cytokine cascade in ARDS.

Study of leukocyte activation and release of toxic mediators during extracorporeal circulation (ECC). ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury.Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury.18 patients who underwent ECC: group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NAC (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h).In group 2, the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreatment prevented an increase in plasma neutrophil elastase activity (18.9 +/- 6.9 vs 49.9 +/- 5.6 ng/ml in group 1 at the end of ECC; p = 0.027). Release of myeloperoxidase (MPO) was not affected (group 1:1105 +/- 225 ng/ml vs group 2:1127 +/- 81 at the end of ECC; p = 0.63). At the end of ECC, total antigenic human neutrophil elastase (group 1:671 +/- 72 ng/ml vs group 2:579 +/- 134; p = 0.37) and complex formation between elastase and alpha 1-proteinase inhibitor were no different in the two groups. There were no significant difference in cellular composition and mediators in the lavage fluid, although values for total number of neutrophils, elastase, MPO and interleukin-8 were lower in group 2.Pretreatment with NAC may prevent lung injury by diminishing elastase activity. Since the release of mediators, especially MPO, is not affected, this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment.

1. The presence of histamine and tryptase in serum during and after coronary artery bypass grafting may be an indication of the induction of inflammation. 2. One group of patients received no glucocorticoids and a second group received methylprednisolone before extracorporeal circulation. In the steroid group no effects were seen on the basal levels of histamine (2.84 + 0.12 ng/ml) and tryptase (030 + 0.05 ng/ml) during and after surgery. In the other group two peak levels of histamine were observed: one at 10 min after starting extracorporeal circulation (4.19 +1.79 ng/ml) and another at 4h after surgery (8.26 +4.85 ng/ml). In this group tryptase was only elevated during the period of extracorporeal circulation (1.54+ 0.16 ng/ml). 3. There were no differences between the two groups in complement activation. C3a levels rose to 170 +8% and 180 +10% of the initial value in the steroid and non-steroid group, respectively. 4. It was concluded that during surgery mast cells were activated, but since tryptase levels decreased in the post-operative period, the second increase in the histamine level can be explained by activation of basophils or by an unknown mechanism for the release of histamine but not tryptase by mast cells. 5. In the bronchoalveolar lavage fluid the levels of histamine and tryptase showed no differences between the two groups of patients, but histamine was enhanced compared with normal levels.

An extensive search for a genetic pattern in Klippel-Trenaunay syndrome (KTS) revealed two other cases of KTS in the families of two of the 86 patients with this vascular syndrome who were questioned. Patients with KTS also had family members with other malformations: e.g. hemihypertrophy in one family, and a prevalence of 7/400 of naevi flammei in first-degree relatives of KTS patients was observed. We suggest that KTS can be inherited in a multifactorial way and a range of vascular malformations can be observed in the family members of patients with this syndrome.

For many decades lead has been considered to be one of the causes of chronic renal failure. A critical analysis of the available epidemiological studies, however, indicates that the relationship between lead exposure and the development of chronic renal failure is largely circumstantial. Indeed, several aspects remain obscure: relative and absolute risk, risk factors, duration of exposure, pathology and diagnostic criteria. Moreover, methodological problems related to cohort selection (i.e. the 'Healthy worker effect'), study design and definition of renal dysfunction may limit the value of the epidemiological results. Although the available literature suggests that lead may play a direct or contributory role in the development of chronic renal failure it is concluded that additional detailed epidemiological studies are required.

An elevation in the serum creatine kinase (CPK) level (without a simultaneous rise in the MB fraction or massive ischaemic cerebral infarction) correlates with the extent of muscular damage. Although usually asymptomatic, it could evolve into a life-threatening condition of rhabdomyolysis complicated by acute renal failure and/or disseminated intravascular coagulation. Critically ill patients may present with an elevated CPK for a number of different reasons. We performed an observational prospective pilot study during 31 days in a mixed ICU in a tertiary referral teaching hospital in order to study the incidence of elevated CPK levels and its possible influence on outcome.