Meconium aspiration syndrome induces complement-associated systemic inflammatory response in newborn piglets

The pathophysiology of meconium aspiration syndrome (MAS) is complex. We recently showed that meconium is a potent activator of complement. In the present study, we investigated whether the complement activation occurring in experimental MAS is associated with a systemic inflammatory response as judged by granulocyte activation and cytokine and chemokine release. MAS was induced by the instillation of meconium into the lungs of newborn piglets (n = 8). Control animals (n = 5) received saline under otherwise identical conditions. Haemodynamic and lung dynamic data were recorded. Complement activation, revealed by the terminal sC5b-9 complex (TCC), and cytokines [interleukin (IL)-6 and IL-8] were measured in plasma samples by enzyme immunoassays. The expression of CD18, CD11b and oxidative burst in granulocytes was measured in whole blood by flow cytometry. Plasma TCC increased rapidly in the MAS animals in contrast with controls (P < 0.0005). The TCC concentration correlated closely with oxygenation index (r = 0.48, P < 0.0005) and ventilation index (r = 0.57, P < 0.0005) and inversely with lung compliance (r = -0.63, P < 0.0005). IL-6 and IL-8 increased in MAS animals compared with the controls (P = 0.002 and P < 0.001, respectively). Granulocyte oxidative burst declined significantly in the MAS animals compared with the controls (P < 0.02). TCC correlated significantly with IL-6 (r = 0.64, P < 0.0005) and IL-8 (r = 0.32; P = 0.03) and inversely with oxidative burst (r = -0.37; P = 0.02). A systemic inflammatory response associated with complement activation is seen in experimental MAS. This reaction may contribute to the pathogenesis of MAS.     

NSAIDs: Learning new tricks from old drugs

Nonsteroidal anti‐inflammatory drugs (NSAIDs) comprise a heterogeneous group of pharmacological agents used for the symptomatic treatment of fever, pain, and inflammation. Although the main mechanism of action of NSAIDs consists of inhibiting prostaglandin synthesis by blocking the enzyme cyclooxygenase (COX), clinical, and experimental data strongly indicate the existence of additional mechanisms. Some of the COX‐independent effects are related to the ability of NSAIDs to penetrate biological membranes and disrupt important molecular interactions necessary for a wide array of cellular functions, including cell adhesion. These effects, in particular those that interfere with l ‐selectin function in neutrophils during the inflammatory response, may contribute to the anti‐inflammatory properties that NSAIDs exert in vivo. Recent contributions in this field have shown that the anti‐l ‐selectin effect of NSAIDs is related to the NADPH‐oxidase‐dependent generation of superoxide anion at the plasma membrane. These findings might represent a novel approach for developing new and effective anti‐inflammatory compounds with a better safety profile than the currently available NSAIDs.     

Quinolones for brucellosis: treating old diseases with new drugs

Although quinolones are theoretically interesting candidates for the treatment of brucellosis, the existing data concerning their efficacy are limited and conflicting. A number of small clinical studies with combination regimens that include quinolones have shown adequacy, but not superiority, although cost-effectiveness, excluding certain disease complications, is an important issue. The emergence of quinolone resistance and its implications is another drawback. Experimental data have yielded contradictory results, although most studies do not indicate a bactericidal effect for quinolones. However, in-vitro studies contrast repeatedly with the clinical response, both in terms of clinical failure, despite in-vitro success, and vice versa.     

Angioedema induced by cardiovascular drugs: new players join old friends

During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin–angiotensin–aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care.     

Immunological tolerance: new approaches using transgenic mice

Transgenic technology allows the introduction into the germline of an animal of a known gene coding for a normally foreign antigen, and by means of a specific promoter, the direction of its expression to specific tissues. The antigen is therefore synthesized by the animal as an authentic self molecule, at a particular stage in development, and in a particular site. In this review, J.F.A.P. Miller and colleagues discuss this radically new approach to the investigation of the mechanism of acquired immunological tolerance to self components.     

Anti-inflammatory treatment of meconium aspiration syndrome: Benefits and risks

Meconium aspiration syndrome (MAS) is a major cause of respiratory insufficiency in the term and post-term newborns. There are several pathomechanisms participating in this disorder, particularly the airway obstruction, surfactant dysfunction, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction. Inflammatory changes resulting from meconium aspiration cause severe impairment of lung parenchyma and surfactant, and influence the reactivity of both vascular and airway smooth muscle. Therefore, anti-inflammatory drugs may be of benefit in the management of MAS. This article reviews the pharmacological actions and side effects of various anti-inflammatory drugs used up to now in the experimental models of MAS and in the treatment of newborns with meconium aspiration.     

Fine-needle aspiration diagnosis of Hodgkin lymphoma using current WHO classification--re-evaluation of cases from 1999-2004 with new proposals

With the advent of modern therapy, the differences in prognoses and treatment regimens among different subtypes of Hodgkin lymphoma (HL) have largely vanished. Stage and the presence of systemic symptoms are much more important than histologic subtypes as predictive factors. The current (2001) WHO classification markedly de-emphasizes spatial relationships as critical to the diagnosis of lymphoma and emphasizes cell morphology, immunophenotype, genetic features, and clinical information to define the disease states. This classification, thus, greatly enhances the capability of fine-needle aspiration (FNA) to accurately diagnose HL. We searched all the FNA cases in our institute in years 1999 through 2004 and found 42 cases, for which 13 were primarily diagnosed (31.0%), 2 were recurrent (4.8%), 5 were highly suspicious (11.9%), and 22 were suspicious (52.3%) for HL. On follow-up tissue biopsy, all the primarily diagnosed, recurrent, and highly suspicious cases were confirmed to be HL (100% agreement). For the 22 suspicious cases, 13 were HL (59.1%), 5 were other lymphomas (22.8%), 1 was lymphoma unclassifiable (4.5%), and 3 were reactive processes (13.6%). The effect of immunostains on the diagnosis of HL was examined, and its importance was emphasized. Analysis of demographic data and the distribution of HL subtypes demonstrate that the study sample is representative of the general HL patient population. On the basis of these results, we propose: (1) If the FNA diagnosis of HL is confirmed both by morphology and immunostains, no further tissue confirmation, subclassification and grading is necessary, and appropriate treatment regimens should follow. (2) The nodular lymphocyte predominant HL and classical HL can be differentiated by adequate immunostaining. (3) If a definitive diagnosis cannot be achieved by FNA, a second FNA or a tissue biopsy should be recommended.