Paradoxical arterial embolism involving both upper extremities in a patient with pulmonary embolism and a patent foramen ovale.

Paradoxical embolization is an uncommon but devastating complication of pulmonary embolism (PE). Awareness of this complication with prompt recognition and treatment could serve to preclude significant disability and death. Described is a case of PE associated with paradoxical embolism to the arteries of both upper extremities. While patent foramen ovale (PFO) is common, paradoxical embolism is infrequent but can involve almost any artery of the body. Discussed are the risk factors, clinical presentations, and diagnostic and treatment options for paradoxical embolism. Awareness of the potential for paradoxical embolization in patients with PE is essential to its prompt recognition and treatment.

High-flow transtracheal insufflation treats obstructive sleep apnea. A pilot study.

To determine the effect of transtracheal insufflation (TTI) on obstructive sleep apnea (OSA), we examined breathing patterns in five tracheostomized patients with OSA at varying TTI flow rates when breathing with a closed tracheostomy. The breathing patterns and polysomnographic responses to air insufflation were studied as TTI was increased from 0 to 15 L/min for brief periods of non-rapid eye movement (NREM) sleep (Experiment 1). The frequency of sleep-disordered breathing episodes remained high at 0 and 5 L/min (87.0 +/- 33.7 and 79.4 +/- 24.4 episodes per hour NREM) and decreased significantly to 41.3 +/- 31.5 and 43.4 +/- 31.4 episodes/h NREM sleep at rates of 10 and 15 L/min, respectively (p = 0.003). At high levels of TTI (10 and 15 L/min), obstructive apneas and hypopneas decreased but periodic laryngeal obstructions were induced during stage 1 NREM sleep. To prevent laryngeal obstructions, a servo-control system was used to briefly interrupt TTI during these events. When this system was implemented for more prolonged periods of sleep (Experiment 2, total sleep time 176.6 +/- 12.5 min), high-flow TTI (hf-TTI, 15 L/min) led to an overall reduction in the combined frequency of obstructive apneas and laryngeal obstructions from 63.8 +/- 21.8 to 10.7 +/- 9.1 (p < 0.03) and was associated with a marked reduction in arousal frequency from 60.0 +/- 26.0 to 8. 3 +/- 5.4/h in NREM sleep, and from 67.5 +/- 3.5 to 0 +/- 0/h in rapid eye movement (REM) sleep. Our findings demonstrate that hf-TTI stabilized breathing patterns in apneic patients, and was safe and efficacious for prolonged periods of sleep.

Pulmonary infiltrates after cytokine therapy for stem cell transplantation. Massive deposition of eosinophil major basic protein detected by immunohistochemistry.

Interleukin-2 (IL-2), a product of activated T-cells, is now being used in a number of protocols for cancer immunotherapy. In one stem cell transplantation protocol for breast cancer, IL-2 is used together with interferon-gamma (IFN-gamma) and cyclosporine to stimulate a graft-versus-tumor response and improve the likelihood of a prolonged remission. We present the case of a patient who developed peripheral eosinophilia, perihilar infiltrates, and hypoxemia after autologous stem cell transplantation and the use of recombinant IL-2 and IFN-gamma. Histologic analysis of transbronchial lung biopsies demonstrated a few eosinophils within the bronchial submucosa. Immunostaining using antibodies directed against eosinophil major basic protein (MBP), however, revealed massive extracellular deposition of this toxic granule protein throughout the lung parenchyma. IL-2 therapy is well known to induce a peripheral eosinophilia and to be associated with the capillary leak syndrome characterized by weight gain, edema, and oliguria. The findings noted in this case report suggest that the eosinophil activation that accompanies immunologic therapy with IL-2 can result in direct toxicity to the lung and a localized vascular leak syndrome. This syndrome should be considered in the differential diagnosis of pulmonary infiltrates that occur acutely after bone marrow transplantation with cytokine augmentation.

Modeling hypersomnolence in sleep-disordered breathing. A novel approach using survival analysis.

The etiology of excessive daytime sleepiness in patients with sleep-disordered breathing (SDB) is not well defined. In this study, we examined the relationships between several clinical and polysomnographic parameters and the degree of hypersomnolence in 741 patients with SDB (apnea-hypopnea index [AHI] >/= 10 events/h). The study sample was obese (body mass index [BMI]: 35.3 +/- 8.5 kg/m2) and had evidence of moderate SDB (AHI: 47.6 +/- 29.3 events/h). Hypersomnolence was quantified with the multiple sleep latency test (MSLT) and survival analysis was used to assess the risk factors for hypersomnolence. In a multivariate proportional hazards model, AHI and nocturnal hypoxemia were independent predictors of hypersomnolence (MSLT < 10 min). The adjusted relative risks (RR) of hypersomnolence were 1.00, 1.30, and 1.65 for patients with an AHI of 10 to 29.9, 30 to 59.9, and >/= 60 events/h, respectively. A positive association between hypersomnolence and oxyhemoglobin desaturation (DeltaSaO2) was observed with RR of 1.00, 1.18, 1.43, and 1.94 for a DeltaSaO2 of 15%, respectively. Sleep fragmentation, as assessed by the distribution of sleep stages, was also an independent predictor of hypersomnolence. Using stage 1 sleep as a reference, an increase in stage 2 and slow wave sleep (SWS) were protective from hypersomnolence. For a 10% increase in stage 2 or SWS the adjusted RR for hypersomnolence were 0.93 and 0.79, respectively. REM sleep showed no significant association with the degree of hypersomnolence. These results suggest that AHI, nocturnal hypoxemia, and sleep fragmentation are independent determinants of hypersomnolence in SDB.

Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice.

The functional role of interleukin (IL)-4 in the development of airway hyperresponsiveness (AHR) and pulmonary eosinophilia in response to sensitization and challenge of mice with sheep red blood cells (SRBC) was examined. Control- and SRBC-sensitized A/J mice were treated with an antibody to the murine IL-4 receptor (anti-IL-4R) 3 days before intratracheal challenge with the antigen or vehicle only. Blockade of IL-4R significantly reduced antigen-induced AHR and prevented increases in goblet cells and bronchoalveolar lavage (BAL) eosinophils. Treatment with anti-IL-4R did not affect antigen-induced increases in lung mRNA and BAL protein levels of IL-5 and interferon-gamma or IL-4 mRNA but did significantly increase IL-4 protein levels. Antigen-induced AHR was not reduced by treatment with antibodies to the adhesion molecules, vascular cell adhesion molecule-1 and very late activation antigen-4. Administration of IL-4 over a 7-day period did not increase airway reactivity or induce any changes in BAL cell numbers in naive mice. These results demonstrate that IL-4 is necessary for in vivo development of antigen-induced AHR, goblet cell metaplasia, and pulmonary eosinophilia.

Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice.

Allergic asthma is characterized by airway hyperresponsiveness and pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the expression of Th2 cytokines and their associated responses, including eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have previously shown in a murine model that antigen-induced increases in airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell dependent. We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression. Sensitized A/J mice developed airway hyperresponsiveness and increased numbers of BAL eosinophils and other inflammatory cells after single or repeated intratracheal challenges with sheep red blood cell antigen. Pulmonary mRNA and protein levels of the Th2 cytokines IL-4 and IL-5 were increased after antigen challenge. Administration of IL-12 (1 microgram/d x 5 d) at the time of a single antigen challenge abolished the airway hyperresponsiveness and pulmonary eosinophilia and promoted an increase in interferon (IFN) gamma and decreases in IL-4 and IL-5 expression. The effects of IL-12 were partially dependent on IFN-gamma, because concurrent treatment with IL-12 and anti-IFN-gamma monoclonal antibody partially reversed the inhibition of airway hyperresponsiveness and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation. These data show that antigen-induced airway hyperresponsiveness and inflammation can be blocked by IL-12, which suppresses Th2 cytokine expression. Local administration of IL-12 may provide a novel immunotherapy for the treatment of pulmonary allergic disorders such as atopic asthma.