Ibrahim Faruqi

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-&bgr;1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle &agr;-actin (&agr;-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-&bgr;1 dose. Fluorescent staining showed &agr;-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and &agr;-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial–mesenchymal transition.

Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome, also known as hantavirus cardiopulmonary syndrome, is a recently described infectious syndrome found throughout the Americas. Although infection is sporadic and uncommon compared with other atypical pneumonia syndromes, its high mortality rate warrants the maintenance of a high index of suspicion in rural settings. Because no specific therapies are available for the disease, prevention and early recognition play an important role in reducing mortality from the disease. This article reviews the nature of the viruses that cause hantavirus pulmonary syndrome, the epidemiology and ecology of disease transmission, and disease recognition, treatment, and prevention.

Targeted Delivery of Amikacin into Granuloma

RATIONALE Nontuberculous mycobacterial (NTM) infection is a growing problem in the United States and remains underrecognized in the developing world. The management of NTM infections is further complicated by several factors, including the need to use high systemic doses of toxic agents, the length of therapy, and the development of drug resistance. OBJECTIVES We have evaluated the use of monocyte-derived dendritic cells (DCs) as a delivery vehicle for a luminescent derivative of amikacin prepared by conjugation to fluorescein isothiocyanate (FITC) (amikacin-FITC) into granulomas formed in the tissues of mice infected with Mycobacterium avium. METHODS Amikacin-FITC was prepared and quantitative fluorescence was used to track the intracellular uptake of this modified antibiotic. The antibiotic activity of amikacin-FITC was also determined to be comparable to unmodified amikacin against M. avium. Amikacin-FITC-loaded DCs were first primed with M. avium, and then the cells were injected into the tail vein of infected mice. After 24 hours, the mice were sacrificed and the tissues were analyzed under fluorescence microscope. MEASUREMENTS AND MAIN RESULTS We found that we were able to deliver amikacin into granulomas in a mouse model of disseminated mycobacterial infection. No increase in levels of monocyte chemoattractant protein-1 and its CCR2 as markers of inflammation were found when DCs were treated with amikacin-FITC. CONCLUSIONS DC-based drug delivery may be an adjunct and useful method of delivering high local concentrations of antibiotics into mycobacterial granulomas.

Acute respiratory distress syndrome: time to entertain a change but not to make one.

ew conditions that form thebackbone of day-to-day inten-sive care unit care have beenreferred to as “an importantpublic health problem.” Certainly, severesepsis must deserve that designation, giventhat there are more than three fourths of amillion cases per year, but what other com-mon ICU problems may qualify? In thisissue of

Short-term outcomes of pulmonary embolism: A National Perspective

Pulmonary embolism (PE) is associated with significant morbidity and mortality in hospitalized patients. Real time data on 90‐day mortality, bleeding, and readmission is sparse.

The Utility of the “Shred Sign” in the Diagnosis of Acute Respiratory Distress Syndrome Resulting from Multifocal Pneumonia

resulting from Multifocal Pneumonia. Abhishek Biswas M.D., Jorge E. Lascano M.D., Hiren J. Mehta M.D., Ibrahim Faruqi M.D., M.P.H. Division of Pulmonary and Critical Care Medicine, University of Florida, 1600 SW Archer Road, Room M452, Gainesville, FL 32610-0225 Corresponding author: Abhishek Biswas Fellow, Division of Pulmonary and Critical Care Medicine, University of Florida, 1600 SW Archer Road, Room M452, Gainesville, FL 32610-0225 Email: abiswas@ufl.edu Tel: 352-273-8734 Fax: 352-273-9154 Running title: Clinical utility of Fractal sign None of the authors have any conflict of interest to declare. Word count: 464 words

1751: ACUTE EMPHYSEMATOUS GASTRITIS AND MULTIORGAN DYSFUNCTION CAUSED BY SARCINA IN A HEALTHY ADULT

Learning Objectives: We report a case of a previously healthy 38 year old man who presented with abdominal pain, pneumobilia and sepsis and underwent emergent gastric wedge resection for acute Emphysematous Gastritis (EG). Examination of surgical specimens revealed significant overgrowth with Sarcina bacteria. To our knowledge, this is the only report of EG caused by Sarcina species. Methods: A 38 year old healthy man presented to an outside hospital with abdmonial pain. Initial imaging with CT scan was unremarkable. Despite IV hydration, his symptoms continued to worsen with metabolic acidosis and leukocytosis. Repeat CT scan revealed pneumobilia, distended stomach, and significant airspace disease. He was given broad-spectrum antibiotics and transferred to our hospital, where he was intubated and underwent emergent gastric wedge resection. His post-operative ICU course was complicated by septic shock requiring vasopressors, prolonged intubation, ARDS, persistent fevers, TPN, a DVT, and ICU delirium. He ultimately recovered and tolerated an enteral diet. He was transferred from ICU post-op day 13 and to acute rehab. Results: EG is a rare and very serious infection of the stomach wall caused by gas-forming organisms and resulting in transmural infarction of the stomach wall, with a mortality rate of 55% based on the 39 case reports that have been published. Sarcina is a genus of gram positive, anaerobic bacteria in the Clostridium cluster. They are known to cause significant gastric pathology in veterinary medicine and are increasingly recognized as a potentially pathogenic organism in humans. Only 22 case reports of Sarcina infection in humans have been reported, but the majority of these have come since 2011, with most cases causing only mild gastrointestinal symptoms. Our hypothesis as to how our patient developed EG secondary to Sarcina infection was by ingestion of contaminated venison. He is a hunter who had eaten days-old, unrefrigerated deer meat prior to the onset of his illness. After consumption of the meat, and before hospitalization, the patient began complaining of gastroenteritis-symptoms.

A 41-Year-Old Woman With Shortness of Breath and History of Rash and Recurrent Laryngeal Edema

A 41-year-old Hispanic woman with a 20 pack-year smoking history presented with worsening shortness of breath on exertion that gradually started 2 years ago, then significantly deteriorated over the last 4 months. She was diagnosed with COPD 2 months prior to her presentation and started on treatment with fluticasone propionate and albuterol. Her medical history was relevant for undifferentiated connective tissue disorder diagnosed 5 years prior due to a positive antinuclear antibody test, arthralgia, recurrent urticarial skin rash, peripheral neuropathy, abdominal pain, and diffuse body swelling. She was started on treatment with prednisone and azathioprine at the time and had substantial improvement in the occurrence of her urticaria. She also had a history of recurrent laryngeal edema of unclear etiology. She had no history of IV drug abuse, no exposure to animals, was not sexually active, and had no recent travel outside of Florida. There was no significant family history of lung diseases.