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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.

Neurally Adjusted Ventilatory Assist (NAVA) offers synchronized proportional pressure in accordance with the electrical activity of the diaphragm (EAdi). NAVA relies on the EAdi to trigger the respiratory cycle and then adjusts the ventilatory assist to the neural drive. The technique necessitates a catheter with bipolar microelectrodes positioned near the crural diaphragm where this signal can be captured. Capturing a reliable EAdi signal is a condition sine qua non for using NAVA as a mode of ventilation. The displayed signal represents the sum of the electrical activity of the muscle action potential of the diaphragm and is expressed in microvolts.A technical note illustrated by a case series in the intensive care unit (ICU) of a tertiary referral hospital with experience using NAVA.Here, we report on three separate cases in which the use of an intra-aortic balloon catheter, a pacemaker and a heating device all resulted in a distortion of the EAdi signal, despite good positioning of the catheter. In a fourth case, we observed internal interference from leaking cardiac electrical activity due to the malpositioning of the EAdi catheter in a patient with atrial fibrillation.We illustrate that the detection and therefore interpretation of the EAdi signal during NAVA can be influenced by mechanical and electrical interference by other equipment used in the ICU or from endogenous leaking cardiac activity.

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.

The first influenza pandemic of the 21st century started in April 2009 with an outbreak of swine origin influenza A(H1NI)2009 in Mexico and the United States. While generally a mild disease affecting mostly school-aged children and young adults, most attention went to severe cases of pneumonia in young previously healthy individuals or individuals belonging to a risk group. In this article we review the literature on the presentation and management of severe cases of influenza A(H1N1)2009 in the intensive care unit (ICU), and describe our own experience in a tertiary referral centre with ECMO facilities. Pregnant women and (bone marrow) transplant patients are two known risk groups for severe influenza described more thoroughly in this paper.These severely ill patients are characterized by respiratory failure, resulting often in the need of mechanical ventilation. As Oseltamivir resistance remains low up till now, early antiviral therapy with Oseltamivir is warranted in these cases. Despite pharmacological and ventilator management, refractory hypoxaemia is described frequently in these patients, with need for rescue therapies like nitric oxide inhalation, high frequency ventilation, and extracorporeal membrane oxygenation. The value of the use of corticosteroids is under discussion. Despite advances in management strategies, mortality and morbidity in these severe cases remains high. In the first influenza season after the pandemic, winter 2010/2011, influenza A(H1N1)2009 is the major influenza A strain in Europe, resulting in reports with increased mortality and morbidity compared to pre-pandemic seasonal influenza. "Continuing vigilance for severe influenza in patients not belonging to the classical influenza risk group might still be warranted for the upcoming influenza season".

A bacteria-free supernatant of Pseudomonas aeruginosa induces the production of neutrophil chemotactic activity in human bronchial epithelial cells in vitro that is due to the potent chemotactic factor, interleukin-8 (IL-8). Because P. aeruginosa supernatant itself is not chemotactic, we hypothesized that intratracheal P. aeruginosa induces the production of neutrophil chemotactic factors, including IL-8, in vivo. Because neutrophils play a key role in cystic fibrosis, inhibition of neutrophil recruitment might be therapeutic. We studied the effect of P. aeruginosa supernatant in the isolated tracheal segment of dogs in vivo, and we measured neutrophil chemotactic activity in vitro in the tracheal fluid. We also determined the local effect of intratracheal administration of leumedin NPC 15669, an inhibitor of neutrophil recruitment, on IL-8- and Pseudomonas-induced neutrophil accumulation. P. aeruginosa supernatant and IL-8 both caused time-dependent accumulation of neutrophils in the tracheal fluid. Tracheal fluid obtained after P. aeruginosa administration had neutrophil chemotactic activity in vitro that was significantly inhibited by the IL-8 antibody. Intratracheal NPC 15669 prevented both IL-8- and Pseudomonas-induced accumulation of neutrophils. We conclude that P. aeruginosa supernatant recruits neutrophils into the airway indirectly by inducing the production of chemotactic factors, including IL-8. Our results suggest a potential therapeutic role for leumedins in chronic airway diseases.

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460GA mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

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 neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.

Besides its effects on tumour cells, tumour necrosis factor (TNF) also acts on a variety of other cells, thus enhancing inflammatory and immune processes. In view of the prominent role of the mast cell in such processes, the aim of the present study was to assess the effects of recombinant TNF-alpha on human mast cells. Mast cells from the infant foreskin obtained during circumcision were dispersed by an enzymatic technique using collagenase and hyaluronidase. Cells thus obtained were pooled, washed and separated by Percoll gradient centrifugation. Mast cells, with a purity of 70-90% were incubated for 60 min with 10(-11) to 10(-7) M rTNF-alpha. Histamine and tryptase levels were assessed in the cell supernatant by spectrofluorometry and radioimmunoassay (RIA) respectively. A concentration dependent release of histamine was observed, which reached a maximum of 11.5 +/- 2.2 nmol/10(6) cells at 10(-8) M rTNF. Release of tryptase was also concentration dependent and reached a maximum of 293 +/- 105 mU/10(6) cells (10(-8) rTNF). rTNF-alpha thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.

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.

Cerebral fat embolism syndrome is a rare, but potentially lethal, complication of long bone fractures. Neurological symptoms are variable, and the clinical diagnosis is difficult. The purpose of this case study is to demonstrate the value of diffusion-weighted MRI of the brain for early diagnosis of fat embolism syndrome. Case Description- A non-head-injured 18-year-old woman suffered acute mental status changes 21 hours after an uncomplicated fracture of the left tibia. MRI of the brain was performed 48 hours after injury. T2-weighted images showed multiple nonconfluent areas of high signal intensity, which, on the diffusion-weighted scans, were revealed as bright spots on a dark background ("starfield" pattern). We suggest that this indicates areas of restricted diffusion that are due to cytotoxic edema, resulting from multiple microemboli.High-intensity lesions in the brain on diffusion-weighted images may serve as an early-appearing and more sensitive indicator of the diagnosis of fat embolism in the clinical context of long bone injury without head trauma.

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.

Rat alveolar macrophages incubated with recombinant rat interferon-gamma produce L-arginine-dependent nitric oxide, which is rapidly decomposed into nitrite: this production by interferon-gamma was markedly enhanced by granulocyte-macrophage colony-stimulating factor and muramyldipeptide, but not by other cytokines. The enhancement was dependent on the presence of L-arginine in the incubation medium. It was based on a simple synergism between interferon-gamma and muramyldipeptide and a priming effect of granulocyte-macrophage colony-stimulating factor for interferon-gamma-induced nitrite production. These data suggest that cytokine networks are important in the induction of nitric oxide in rat alveolar macrophages.

Immunostimulated peritoneal macrophages of mice and rat have been demonstrated to produce L-arginine-derived nitrogen oxides. This metabolic pathway has also recently been found in rat alveolar macrophages and is suggested to play a certain role in lung injury. In vitro nitrite production from alveolar macrophages stimulated in vitro with lipopolysaccharide and recombinant interferon-gamma was inhibited by the addition of the irreversible serine-protease inhibitors, N-tosyl-L-phenylalanine chloromethyl-ketone (3 x 10(-7)-3 x 10(-4) M) and N-tosyl-L-lysine chloromethyl-ketone (3 x 10(-7)-3 x 10(-4) M) in a concentration-dependent manner. Two reversible inhibitors, N-alpha-p-tosyl-L-arginine methyl ester hydrochloride and benzoyltyrosine ethyl ester, were also effective but to a lesser extent. These antiproteases provide an opportunity to study the modulating influence on this recently discovered inflammatory pathway in alveolar phagocytic cells.

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.

An L-arginine-dependent pathway, by which L-arginine is metabolised to citrulline and nitrogen oxides, has been recently identified in some cell types. In cultured rat lung fibroblasts the presence of L-arginine was necessary for the production of nitrite to be induced by rat recombinant interferon-gamma and synergistically enhanced by lipopolysaccharide and interleukin-1beta. Lipopolysaccharide and interleukin-1beta did not induce nitrite biosynthesis by themselves. Biosynthesis was apparently dependent on tetrahydrobiopterin, since it could be blocked by diaminohydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis. Dexamethasone blocked nitrite production by a receptor-mediated mechanism. These data indicate that rat lung fibroblasts express an L-arginine-dependent nitric oxide synthase which can be induced by some mediators of inflammation.

Mast cells from infant foreskin obtained during circumcision were dispersed by an enzymatic technique, pooled, washed and purified. Mast cells, with a purity of 70–90% were incubated with 10−11 to 10−7M rTNFα. Histamine and tryptase levels were assessed in the cell supernatant and a concentration dependent release of histamine was observed. Histamine reached a maximum of 11.5±2.2 nmol/106 cells at 10−8M rTNF. Tryptase reached a maximum of 293±105 mU/106 cells (10−8M rTNF). rTNFα thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.

The aortic arch syndrome characterised by diminished or absent pulses in the arteries arising from the aortic arch has many etiologies, such as syphilitic aortitis, dissection of the aorta, atherosclerosis and Takayasu's arteritis. The diagnostic criteria of Takayasu's arteritis often do not mention histological investigations. We observed a case of an aortic arch syndrome, presenting as a classical case of Takayasu's arteritis but caused by a severe form of atherosclerosis.

Pentachlorophenol (PCP) is a widely applied insecticide and fungicide, particularly in wood preservation. Significant amounts of this compound have been reported in human serum, adipose tissue and urine. PCP is even found in people not occupationally exposed to this toxin or not living in PCP-treated log-houses. Substantial concentrations of this possible neurotoxic agent were detected in the cerebrospinal fluid (CSF) of 16 neurologic patients as measured by a high resolution gas chromatographic method using electron capture detection. This is the first report on PCP levels in (human) CSF. The observed level in CSF ranged from 0.24 up to 2.03 micrograms/L (ppb), with an average value of 0.75 +/- 0.49. The cerebrospinal fluid level did not correlate with the serum PCP concentration nor with the protein level of the cerebrospinal fluid.

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.

The occurrence of torsades de pointe is often associated with the use of drugs. We report three cases of amiodarone-induced torsades de pointe. Although a lot of amiodarone-induced torsades de pointe have been published, a review of all these cases and the underlying risk-factors has never been made.

An inc ident is described in which a Belgian farmer , fo l l ow ing a successfui tomato harvest period, purchased 4001 of soli fumigant in two equal and s imi lar containers, which were respect ively labeled "Luxan Monam Concentr › and "Monam BASF". Both vessels were supposed to contain the same s ter i lan t , "Monam | (sodium methy ld i th iocarbamate , CH3.NH. CS.SNa) in equal concentrat ions (510 g /L) as was indicated on the i r labels. Their contents were subsequent ly mixed in equal volumes in a 500 L tank and fumigated into a vegetable greenhouse at about 20 kg/ acre through an automated inbu i l t i r r iga t ion system. Dur ing the mix ing stage, the fa rmer had put on a gas-mask (act ivated charcoal) and protect ive c lo th ing, thus the acr id and tox i c nature of the s ter i lan t remained unnot iced.

Poisoning often affects the ear, nose, mouth and throat. Sialorrhea, stomatitis, oropharyngeal dryness, a burning sensation in the mouth, rhinitis and nasal septal perforation, hearing loss and vestibular disturbances can be the result of intoxications by poisonous plants, growing or used in Europe and the United States. This article has not the intention to be exhaustive, but to give a synopsis of this topic.