Age-specific characteristics of neutrophilic dermatoses and neutrophilic diseases in children.

BACKGROUND: Our suggested 'modern' concepts of 'neutrophilic dermatoses' (ND) and 'neutrophilic disease' were based on observations in adult patients and have not been studied in paediatric patients. Only a minority of ND occurs in children, and little is known about age-specific characteristics. OBJECTIVES: To describe age-specific characteristics of ND in children and to study whether our suggested 'modern' classification of ND may be applied to children. METHODS: We conducted a retrospective multicentre study in a French cohort of 27 paediatric patients diagnosed with pyoderma gangrenosum (PG) or Sweet's syndrome (SS). RESULTS: Demographics and distribution of typical/atypical forms were similar in patients diagnosed with PG and SS. Atypical ND were more frequent in infants (90%), when compared to young children (60%) and adolescents (33%). Neutrophilic disease was observed in 17/27 patients and was most frequent in infants. Neutrophilic disease of the upper respiratory tract, as well as cardiac neutrophilic disease, was only observed in infants, whereas other locations were similarly found in infants, young children and adolescents. In infants and young children, ND were associated with a large spectrum of general diseases, whereas in adolescents associations were limited to inflammatory bowel disease and Behçet's disease. CONCLUSIONS: Our study describes the concept of ND in paediatric patients and shows that they have some characteristics different from ND occurring in adults. ND occurring in infants can be associated with a large spectrum of general diseases. Occurrence of neutrophilic disease is frequent in children. Thus, ND occurring in young paediatric patients should incite clinicians to schedule complementary explorations in order to search for involvement of other organs and to rule out monogenetic autoinflammatory syndromes.

Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses.

Pyoderma gangrenosum, a dramatic ulcerative skin disease, and Sweet syndrome, a papular dermatosis, were described independently. It was subsequently shown that they share many characteristics, including clinical overlap and the frequent association with multisystemic disorders. The group of the neutrophilic dermatoses encompasses these two dermatoses, as well as other conditions having in common an aseptic neutrophilic infiltrate predominating in the epidermis and/or the dermis and/or the subcutis. Some patients also experience neutrophilic infiltrates in other organs, defining the neutrophilic disease. Recent research suggests that the neutrophilic dermatoses could be considered as the cutaneous expression of the autoinflammation, an aberrant hyperproduction of interleukin-1. Autoinflammation is responsible for monogenic diseases, and is also involved in the mechanism of many polygenic conditions, including the neutrophilic dermatoses.

Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it.

A signaling pathway that induces programmed necrotic cell death (necroptosis) was reported to be activated in cells by several cytokines and various pathogen components. The major proteins participating in that pathway are the protein kinases RIPK1 and RIPK3 and the pseudokinase mixed lineage kinase domain-like protein (MLKL). Recent studies have suggested that MLKL, once activated, mediates necroptosis by binding to cellular membranes, thereby triggering ion fluxes. However, our knowledge of both the sequence of molecular events leading to MLKL activation and the subcellular sites of these events is fragmentary. Here we report that the association of MLKL with the cell membrane in necroptotic death is preceded by the translocation of phosphorylated MLKL, along with RIPK1 and RIPK3, to the nucleus.

Comparison of freehand-navigated and aiming device-navigated targeting of liver lesions.

BACKGROUND: Accurate needle placement is crucial for the success of percutaneous radiological needle interventions. We compared three guiding methods using an optical-based navigation system: freehand, using a stereotactic aiming device and active depth control, and using a stereotactic aiming device and passive depth control. METHODS: For each method, 25 punctures were performed on a non-rigid phantom. Five 1 mm metal screws were used as targets. Time requirements were recorded, and target positioning errors (TPE) were measured on control scans as the distance between needle tip and target. RESULTS: Time requirements were reduced using the aiming device and passive depth control. The Euclidian TPE was similar for each method (4.6 ± 1.2-4.9 ± 1.7 mm). However, the lateral component was significantly lower when an aiming device was used (2.3 ± 1.3-2.8 ± 1.6 mm with an aiming device vs 4.2 ± 2.0 mm without). DISCUSSION: Using an aiming device may increase the lateral accuracy of navigated needle insertion.

The extrinsic cell death pathway and the élan mortel.

Early in the exploration of the chemical nature of life, it was widely believed that the molecules of living organisms, by their very nature, differ from those of inorganic material molecules and possess a vital force ('élan vital'). Similarly, early scientific thinking on the subject of cell death and its induction by cytotoxic cells of the immune system was pervaded by a sense that the molecules mediating these functions possess intrinsic deadly activity and are dedicated exclusively to death-related tasks. This impression was also reflected in the initial notions of the mode of action of intracellular proteins that signal for death. It is now gradually becoming clear, however, that proteins participating in death induction also have functions unrelated to death. Nevertheless, as exemplified by studies of the function of caspase-8 (an enzyme that signals both for activation of the extrinsic cell-death pathway and for non-death-related effects), analysis of the mechanistic basis for such heterogeneity might allow identification of distinct structural determinants in the proteins participating in death induction that do bear death specificity.

Caspase-8 deficiency facilitates cellular transformation in vitro.

Caspase-8 is frequently deficient in several kinds of human tumors, suggesting that certain effects of this enzyme restrict tumor development. To examine the nature of the cellular function whose regulation by caspase-8 contributes to its antitumor effect, we assessed the impact of caspase-8 deficiency on cell transformation in vitro. Caspase-8-deficient mouse embryonic fibroblasts immortalized with the SV40 T antigen did not survive when cultured in soft agar, and were nontumorogenic in nude mice. However, the rate of transformation of these cells during their continuous growth in culture, as reflected in the observed emergence of cells that do grow in soft agar and are able to form tumors in nude mice, was far higher than that of cells expressing caspase-8. These findings indicate that caspase-8 deficiency can contribute to cancer development in a way that does not depend on the enzyme's participation in killing of the tumor cells by host immune cytotoxic mechanisms, or on its involvement in the cell-death process triggered upon detachment of the cells from their substrate, but rather concerns cell-autonomous mechanisms that affect the rate of cell transformation.

[Neutrophilic dermatoses]. / Les dermatoses neutrophiliques.

PURPOSE: The neutrophilic dermatoses are a group of skin diseases mainly characterized by an infiltration of the skin by normal polymorphonuclears, without any identifiable (infectious) cause. In this review we describe the main neutrophilic dermatoses and point on their multisystemic dimension. CURRENT KNOWLEDGE AND KEY-POINTS: Well-defined neutrophilic dermatoses are Sweet's syndrome, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum and neutrophilic eccrine hidradenitis, as well as newer and rarer conditions such as aseptic abscesses. Clinical overlap between these disorders led to the concept of "the" neutrophilic dermatosis. In addition, patients with a neutrophilic skin disorder may also suffer from extra-cutaneous aseptic neutrophilic infiltrates. This "neutrophilic disease" is often difficult to diagnose. Neutrophilic dermatoses are significantly associated with systemic disease. These include hematological disorders, inflammatory bowel disease, joint immunological disorders, and other malignant or inflammatory conditions. First-line treatment of acute neutrophilic conditions is steroid therapy. In chronic conditions, dapsone is often efficient. FUTURE PROSPECTS AND PROJECTS: The mechanisms underlying the inappropriate activation of polymorphonuclears are poorly understood. Hematopoietic growth factors and adhesion molecules are believed to play a role in the pathophysiology of the neutrophilic dermatoses.

[1801-2001: two centuries of dermatology and venereology in the Assistance Publique-Hôpitaux de Paris]. / 1801-2001: deux siècles de dermatologie et de vénéréologie à l'Assistance Publique-Hôpitaux de Paris.

The specialization "Dermatology" was born at the Saint-Louis hospital in France in 1801, in the light of the revolutionary reforms that led to fundamental changes in the functioning of the hospitals in Paris. Hence, the Saint-Louis hospital occupies an eminent position in the history of dermatology in France, reinforced by the role of Jean-Louis Alibert, who founded the French school of Dermatology. Despite the place occupied by the physicians of the Saint-Louis Hospital in the creation and development of the French school of dermatology, other physicians in other hospitals contributed to the expansion of the dermatology school. The work of Pierre Rayer, in the nineteenth century, at the Saint-Antoine and subsequently the Charité hospitals, are within this scope. More recently, the re-organization of the Faculty of Medicine into University Hospital Centers has permitted the creation of various treatment, teaching and research centers within the structure of the public hospitals in Paris. From the start, syphilis was part of the Dermatology teaching and practice. In Paris, several so-called "specialized" hospitals were created to house patients presenting with syphilis. Later on, the existence of these hospitals was questioned notably because of the constraints that their functioning imposed on the patients. Anti-venereal care centers were developed in response to the request of the practitioners to facilitate the access to treatment.

Metaphyseal fractures mimicking abuse during treatment for clubfoot.

BACKGROUND: Metaphyseal injuries resembling the classic metaphyseal lesion (CML) of abuse may occur as the result of serial casting during treatment of clubfoot deformity. Mentioned in the orthopedic literature in 1972, this iatrogenic fracture has not been described in the radiologic literature nor has the similarity to injuries occurring with abuse been previously recognized. OBJECTIVE: To describe the mechanism and radiographic appearance of metaphyseal injury observed during serial casting of clubfoot. Note similarities to the CML of abuse. MATERIALS AND METHODS: Eight children ranging in age from 1 to 4 months underwent casting for clubfoot. Five orthopedic surgeons from three different institutions performed the casting. Two patients had spina bifida and one, arthrogryposis. A complete skeletal survey was performed on one child who was abused; there was no suspicion of abuse in the remaining seven. RESULTS: All children manifest injury with periosteal new bone. One child had clear evidence of abuse with 24 rib fractures. X-rays of lower extremities in short leg casts revealed bilateral tibial metaphyseal fractures. Four other children had metaphyseal fractures resembling the CML of abuse, and three developed an area of sclerosis within the metaphysis. CONCLUSION: In the setting of serial casting for equinovarus deformity, metaphyseal injury even the CML of abuse may be noted. Since inflicted injuries are almost always unobserved and explanations rarely offered, the fact that the CML occurs as a result of orthopedic maniuplation may offer some further insight concerning the pathogenesis of this well-described abuse injury.

Evaluating decision rules for nitrogen fertilization.

It is important, both for farmer profit and for the environment, to correctly dose nitrogen fertilizer for crop growth. Fertilizer recommendations are embodied in decision rules, which give a recommended dose of nitrogen (N) as a function of information available at the time the decision is made. In this paper, we first propose a criterion for evaluating decision rules. The proposed criterion is the expectation of the objective function when the decision rule is implemented. The major problem here is the estimation of this criterion. Two estimators are considered, a model-based and a nonparametric estimator. A simulation study shows that, in essentially all cases, the nonparametric estimator is better or no worse than the model-based estimator. The bias in the nonparametric estimator is always very small.