Perthes' or Perthes' resembling disease in 13-month-old boy

Onset of Perthes' disease is reported frequently from the age of 2 years. Latest publications showed cases with onset of this disease in infancy at ages of 17 and 18 months. We report the case of a 13-month-old boy, who presented with left-sided limping. Radiological examination showed reduced height and fragmentation of the femoral head. Magnetic resonance imaging showed the typical signs of an avascular necrosis. Follow-up was done after 3, 7 and 15 months. Plain radiography showed the femoral head in a state of reparation. This is the youngest documented case of Legg-Calvé-Perthes' disease and is discussed under consideration of the current literature.     

Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation

In the acute respiratory distress syndrome, recruitment of peripheral blood monocytes results in expansion of the total pool of resident alveolar macrophages. The fate of resident macrophages, or whether recruited monocytes are selectively eliminated from the alveolar airspace or differentiate into resident alveolar macrophages during the resolving phase of inflammation, has not been determined. Here, we analyzed the kinetics of resident and recruited macrophage turnover within the alveolar airspace of untreated and LPS-challenged mice. Using bone marrow chimeric CD45.2 mice that were generated by lethal irradiation of CD45.2 alloantigen-expressing recipient mice and bone marrow transplantation from CD45.1 alloantigen-expressing donor mice, we employed a flow cytometric approach to distinguish recipient from donor-type macrophages in bronchoalveolar lavage fluids. Our data show that resident alveolar macrophages of untreated chimeric CD45.2 mice are very slowly replaced by constitutively immigrating CD45.1 positive monocytes, resulting in a replacement rate of approximately 40% by 1 yr. In contrast, more than 85% of the resident CD45.2 positive alveolar and lung homogenate macrophages were exchanged by donor CD45.1-expressing macrophages within 2 mo after treatment with Escherichia coli endotoxin (LPS). Importantly, fluorescence-activated cell sorter analysis of increased annexin V binding to both recipient and donor-type macrophages revealed increased apoptotic events to underlie this endotoxin-driven inflammatory macrophage turnover. Collectively, the data show that under baseline conditions the alveolar macrophage turnover exhibits very slow kinetics, whereas acute lung inflammation in response to treatment with LPS triggers a brisk acceleration of recruitment of monocytes that replace the resident alveolar macrophage population.     

The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling

The Grb2 associated binder (Gab) adaptor/scaffolding protein family comprises conserved proteins: mammalian Gab1, Gab2 and Gab3, Drosophila Dos and Caenorhabditis elegans Soc1. Gab adaptors are involved in multiple signaling pathways mediated by receptor- and non-receptor protein tyrosine kinases (PTKs), and become phosphorylated upon stimulation by growth factors-, cytokines-, Ig Fc- and antigen receptors. Through its phosphorylated tyrosine containing motifs, proline-rich sequences and pleckstrin homologue (PH) domain Gab adaptors may generate an interacting platform for proteins with SH2 and SH3 domains and may transfer these molecules to the plasma membrane, thereby contributing to their activation. This review will concentrate on the function of mammalian Gab proteins in the signal transduction triggered by immune receptors.     

Importance of phosphoinositide 3-kinase gamma in the host defense against pneumococcal infection

RATIONALE: The pivotal role of phosphoinositide 3-kinase gamma (PI3Kgamma) in leukocyte recruitment makes it an attractive target for immunomodulatory therapy. However, interfering with PI3Kgamma signaling might increase the risk of bacterial infections in humans. OBJECTIVES: We hypothesized that deletion or pharmacologic inhibition of PI3Kgamma would impair the lung inflammatory response to the prototypic gram-positive bacterial pathogen Streptococcus pneumoniae. METHODS: PI3Kgamma knockout (KO) and wild-type mice were infected with S. pneumoniae or challenged with the pneumococcal virulence factor pneumolysin (PLY), and inflammatory leukocyte recruitment, bacterial pathogen elimination, and resolution/repair processes were determined. MEASUREMENTS AND MAIN RESULTS: PI3Kgamma KO mice challenged with PLY responded with lung edema and neutrophilic alveolitis, but showed a drop in alveolar macrophages and failed to recruit exudate macrophages when compared with wild-type mice. S. pneumoniae-infected PI3Kgamma KO mice and wild-type mice pretreated with the pharmacologic inhibitor AS-605240 recruited similar numbers of neutrophils but substantially fewer exudate macrophages into their lungs than control animals. They also displayed a significantly reduced lung pneumococcal clearance and showed an impaired resolution/repair process, leading to progressive pneumococcal pneumonia. CONCLUSIONS: PI3Kgamma gene deletion or pharmacologic inhibition of PI3Kgamma leads to perturbations of critical innate immune responses of the lung to challenge with S. pneumoniae. These data are of clinical relevance for the treatment of chronic inflammatory diseases where pharmacologic inhibition of PI3Kgamma signaling to attenuate effector cell recruitment may have implications for innate immune surveillance of remote organ systems.     

Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

The nicotinic acetylcholine receptors are prototypic ionotropic receptors that mediate fast synaptic transmission. However, also non-excitable cells, and particularly the tegumental cells that line external and internal body surfaces, express acetylcholine receptors of neuronal type sensitive to nicotine. Bronchial epithelial cells, endothelial cells of blood vessels and skin keratinocytes express neuronal nicotinic receptors composed of alpha(3), alpha(5), beta(2) and beta(4) subunits, similar to those expressed in sympathetic ganglia, and neuronal nicotinic receptors composed of alpha(7) subunits. Neuronal nicotinic receptors in tegumental cells are involved in modulating cell shape and motility, and therefore in maintaining the integrity of the surfaces lined by those cells. Neuronal nicotinic receptors in non-neuronal tissues may modulate other functions, including cell proliferation and differentiation. Acetylcholine is synthesized, secreted and degraded by a variety of cells, including the tegumental cells that express neuronal nicotinic receptors. Thus, acetylcholine may function as a local "hormone" that is able to modulate cell functions that require fast adaptation to new conditions. The presence of neuronal nicotinic receptors sensitive to nicotine in tissues known to be involved in tobacco toxicity, like bronchi and blood vessels, raises the possibility that they mediate some of the toxic effects of smoking.     

Forward displacements of fading objects in motion: the role of transient signals in perceiving position

Visual motion causes mislocalisation phenomena in a variety of experimental paradigms. For many displays objects are perceived as displaced 'forward' in the direction of motion. However, in some cases involving the abrupt stopping or reversal of motion the forward displacements are not observed. We propose that the transient neural signals at the offset of a moving object play a crucial role in accurate localisation. In the present study, we eliminated the transient signals at motion offset by gradually reducing the luminance of the moving object. Our results show that the 'disappearance threshold' for a moving object is lower than the detection threshold for the same object without a motion history. In units of time this manipulation led to a forward displacement of the disappearance point by 175 ms. We propose an explanation of our results in terms of two processes: Forward displacements are caused by internal models predicting positions of moving objects. The usually observed correct localisation of stopping positions, however, is based on transient inputs that retroactively attenuate errors that internal models might otherwise cause. Both processes are geared to reducing localisation errors for moving objects.     

A comparison of breastfeeding rates in an urban birth cohort among women delivering infants at hospitals that employ and do not employ lactation consultants.

OBJECTIVE: To compare rates of breastfeeding at hospital discharge between facilities that employ and do not employ International Board Certified Lactation Consultants (IBCLCs). METHODS: This study used a cross-sectional design. Data from 11,525 birth certificates of Philadelphia residents who delivered in 2003 were used. Breastfeeding was assessed using a question included on the Pennsylvania birth record, "Is the infant being breastfed at discharge?" The Philadelphia Department of Public Health's lactation consultants collected information on number of hours worked annually by IBCLCs by facility. RESULTS: After adjusting for race/ethnicity, education, insurance status, age, marital status, route of delivery, birth weight, and gestational age, delivering in a hospital that employed an IBCLC was associated with a 2.28 (95% confidence interval [CI] =1.98,2.62) times increase in the odds of breastfeeding at hospital discharge. Among women receiving Medicaid, delivering at a hospital that employed IBCLCs was associated with a 4.13 (95% CI =3.22,4.80) times increase in the odds of breastfeeding at hospital discharge. CONCLUSIONS: The findings presented here identify an association between delivering at a facility that employs IBCLCs and breastfeeding at hospital discharge. As the strength of this association is not negligible, particularly for women on Medicaid, these findings may be used to encourage widespread use of IBCLCs.     

Painful metastases involving bone: feasibility of percutaneous CT- and US-guided radio-frequency ablation

PURPOSE: To determine the safety and efficacy of radio-frequency (RF) ablation for pain reduction, quality of life improvement, and analgesics use reduction in patients with skeletal metastases. MATERIALS AND METHODS: Over 10 months, 12 adult patients with a single painful osteolytic metastasis in whom radiation therapy or chemotherapy had failed and who reported severe pain (pain score > or = 4 [scale of 0-10]) over a 24-hour period were treated with percutaneous imaging-guided RF ablation with a multi-tined electrode while under general anesthesia. Patient pain was measured with a Brief Pain Inventory 1 day after the procedure, every week for 1 month, and thereafter every other week (total follow-up, 6 months). Patient analgesics use was also recorded at these follow-up intervals. Follow-up contrast material-enhanced computed tomography was performed 1 week after the procedure. Complications were monitored. Analysis of the primary end point was undertaken with paired comparison procedures. RESULTS: Lesion size was 1-11 cm. Before RF ablation, mean worst pain score in a 24-hour period in 12 patients was 8.0 (range, 6-10). At 4 weeks after treatment, mean worst pain decreased to 3.1 (P =.001). Mean pain before treatment was 6.5 and decreased to 1.8 (P <.001) 4 weeks after treatment. Mean pain interference in general activity decreased from 6.6 to 2.7 (P =.002) 4 weeks after treatment. Eight of 10 patients using analgesics reported reduced use at some time after RF ablation. No serious complications were observed. CONCLUSION: RF ablation of painful osteolytic metastases is safe, and the relief of pain is substantial.