A 62-Year-Old Woman With Diffuse Myalgias, Fatigue, and Shortness of Breath.

CASE PRESENTATION: A 62-year-old woman with a history of partially treated Graves disease and hypertension presented with approximately 3 weeks of worsening fatigue, lower extremity myalgias, and shortness of breath. Her medical history included a thyroid radiofrequency ablation several years earlier. Following the ablation, she was found to have some residual thyroid activity, negating the need for therapy. She was lost to follow-up after months of normal thyroid-stimulating hormone values. On this presentation, the patient was noted to be in atrial fibrillation with a rapid ventricular rate, and although she presented alert and oriented initially, she developed progressive inattentiveness and confusion while in the ED. The patient was transferred to the medical ICU for further management of her rapid heart rate and progressive delirium.

500 Million Alveoli from 30,000 Feet: A Brief Primer on Lung Anatomy.

The lungs are a complex organ that fulfill multiple life-sustaining roles including transfer of oxygen and carbon dioxide between the ambient environment and the bloodstream, host defense, and immune homeostasis. As in any biological system, an understanding of the underlying anatomy is prerequisite for successful experimental design and appropriate interpretation of data, regardless of the precise experimental model or procedure in use. This chapter provides an overview of human lung anatomy focused on the airways, the ultrastructure or parenchyma of the lung, the pulmonary vasculature, the innervation of the lungs, and the pulmonary lymphatic system. We will also discuss notable anatomic differences between mouse and human lungs.

Bedside ultrasound for the interventional pulmonologist.

This article summarizes the current literature regarding thoracic ultrasonography and specifically guides the interventional pulmonologist in use of thoracic ultrasound for practical applications.

IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM) recovered from the lungs of mice undergoing cecal ligation and puncture (CLP) display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3) and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/-) mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

Immunosuppression in sepsis.

The often fatal sepsis syndrome is characterized by the systemic release of inflammatory mediators, which is regulated and counterbalanced by the coordinated expression of anti-inflammatory molecules. The magnitude of sepsis-induced tissue injury and subsequent risk of infectious complications is dictated by the balance between the expression of pro- and anti-inflammatory mediators. As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the profound effects that sepsis and similar states of overwhelming stress have on host innate and adaptive immunity. Impaired leukocyte function in sepsis has important clinical consequences, as high mortality rates have been observed in patients who display evidence of sepsis-induced immune dysregulation. Functional defects in leukocytes isolated from patients with sepsis include diminished expression of important cell surface molecules, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. In this article, we review the current literature supporting the notion that dysregulation of host immunity occurs during sepsis syndrome, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.

Toll-like receptor 9 regulates the lung macrophage phenotype and host immunity in murine pneumonia caused by Legionella pneumophila.

Experiments were performed to determine the contribution of TLR9 to the generation of protective immunity against the intracellular respiratory bacterial pathogen Legionella pneumophila. In initial studies, we found that the intratracheal (i.t.) administration of L. pneumophila to mice deficient in TLR9 (TLR9(-/-)) resulted in significantly increased mortality, which was associated with an approximately 10-fold increase in the number of lung CFU compared to that of wild-type BALB/c mice. Intrapulmonary bacterial challenge in TLR9(-/-) mice resulted in the reduced accumulation of myeloid dendritic cells (DC) and activated CD4(+) T cells. Lung macrophages isolated from Legionella-infected TLR9(-/-) mice displayed the impaired internalization of bacteria and evidence of alternative rather than classical activation, as manifested by the markedly reduced expression of nitric oxide and type 1 cytokines, whereas the expression of Fizz-1 and arginase-1 was enhanced. The adoptive transfer of bone marrow-derived DC from syngeneic wild-type, but not TLR9(-/-), mice administered i.t. reconstituted anti-legionella immunity and restored the macrophage phenotype in TLR9(-/-) mice. Finally, the i.t., but not intraperitoneal, administration of the TLR9 agonist molecule CpG oligodeoxynucleotide stimulated protective immunity in Legionella-infected mice. In total, our findings indicate that TLR9 is required for effective innate immune responses against the intracellular bacterial pathogen L. pneumophila, and approaches to maximize TLR9-mediated responses may serve as a means to augment antibacterial immunity in pneumonia.

Rapid endovascular warming for profound hypothermia.

Profound hypothermia is associated with high mortality and morbidity. Optimal outcomes have been reported with invasive extracorporeal warming techniques not readily available in most hospitals. Endovascular warming devices may provide a less invasive alternative. A 68-year-old woman developed profound hypothermia after environmental exposure. On arrival, she was comatose, severely bradycardic, without palpable pulses, and with a core body temperature of 23.0 degrees C (72 degrees F). Attempts to warm her with traditional methods during 2 hours were ineffective. An endovascular temperature control system was placed and effectively warmed the patient at about 3 degrees C (4.5 degrees F) per hour, with return of hemodynamic stability. When hypothermia is profound, surface warming works poorly and invasive strategies, including cardiopulmonary bypass, are recommended. Rapid warming from profound hypothermia can be accomplished with endovascular systems, and these may be an effective alternative to more invasive extracorporeal methods.