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4.
Pediatr Pulmonol ; 56(9): 2918-2924, 2021 09.
Article in English | MEDLINE | ID: mdl-34219413

ABSTRACT

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased D-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 polymerase chain reaction and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic. Keywords COVID-19 pandemic, EVALI, MIS-C.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome , Adolescent , Humans , Lung Injury/epidemiology , Lung Injury/etiology , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications
5.
Pediatr Pulmonol ; 55(12): 3443-3449, 2020 12.
Article in English | MEDLINE | ID: mdl-32902877

ABSTRACT

Bronchiectasis (BE) is defined as a permanent, irreversible dilation of the bronchial tree. In the pediatric population, this disease process is most commonly associated with patients with cystic fibrosis (CF). However, BE unrelated to CF is increasingly noted as a cause of chronic respiratory related morbidity worldwide. Chronic inflammation and recurrent infection result in cellular cascades that lead to irreversible structural changes of the airways. When these architectural changes occur, they confer extensive risks to morbidity usually due to continued infections. In the adult population, BE has been associated with chronic obstructive pulmonary disease, which is mainly caused by cigarette smoking. In this report, the authors reviewed various cases of BE in the pediatric population at our institution. After a comprehensive case by case review, we compiled details of three cases of newly diagnosed BE where the most likely inciting factor was the electronic cigarette use. Common features of the three cases included at least a year of e-cigarette use with conjunction of tetrahydrocannabinol and radiologic findings of BE, ground glass opacities, and nodule formation.


Subject(s)
Bronchiectasis/chemically induced , Electronic Nicotine Delivery Systems , Adult , Child , Cystic Fibrosis/complications , Humans , Lung/physiopathology , Male , Vaping
6.
Pediatrics ; 145(4)2020 04.
Article in English | MEDLINE | ID: mdl-32217740

ABSTRACT

Idiopathic acute eosinophilic pneumonia is a rare and potentially life-threatening condition that is defined by bilateral pulmonary infiltrates and fever in the presence of pulmonary eosinophilia. It often presents acutely in previously healthy individuals and can be difficult to distinguish from infectious pneumonia. Although the exact etiology of idiopathic acute eosinophilic pneumonia remains unknown, an acute hypersensitivity reaction to an inhaled antigen is suggested, which is further supported by recent public health risks of vaping (electronic cigarette) use and the development of lung disease. In this case, a patient with a year-long history of vaping in conjunction with tetrahydrocannabinol cartridge use who was diagnosed with idiopathic acute eosinophilic pneumonia with associated bilateral hilar lymphadenopathy is described.


Subject(s)
Dronabinol/toxicity , Lymphadenopathy/etiology , Psychotropic Drugs/toxicity , Pulmonary Eosinophilia/etiology , Vaping/adverse effects , Adolescent , Adrenal Cortex Hormones/therapeutic use , Electronic Nicotine Delivery Systems , Female , Humans , Lymphadenopathy/diagnosis , Lymphadenopathy/drug therapy , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/diagnostic imaging , Pulmonary Eosinophilia/drug therapy
8.
Bioorg Med Chem Lett ; 27(4): 1089-1093, 2017 02 15.
Article in English | MEDLINE | ID: mdl-28089701

ABSTRACT

A series of potent and novel acylsulfonamide-bearing triazines were synthesized and the structure-activity relationships (SARs) as HCV entry inhibitors were evaluated. This acylsulfonamide series was derived from an early lead, 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoic acid wherein the carboxylic acid was replaced with an acylsulfonamide moiety. This structural modification provided a class of compounds which projected an additional vector off the terminus of the acylsulfonamide functionality as a means to drive activity. This effort led to the discovery of potent analogues within this series that demonstrated sub-nanomolar EC50 values in the HCV pseudotype particle (HCVpp) assay.


Subject(s)
Antiviral Agents/pharmacology , Hepacivirus/drug effects , Membrane Fusion/drug effects , Triazines/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Hepacivirus/physiology , Humans , Rats , Structure-Activity Relationship , Triazines/chemistry , Triazines/pharmacokinetics
9.
Bioorg Med Chem ; 10(5): 1381-98, 2002 May.
Article in English | MEDLINE | ID: mdl-11886802

ABSTRACT

The need for imaging agents for estrogen receptor positive (ER+) tumors that are both cost effective and widely available, as well as the need for novel radiotherapeutic agents for the treatment of breast cancer, has prompted us to investigate cyclopentadienyl tricarbonyl metal [CpMet(CO)(3), Met=Re, Tc-99m] complexes that bind well to the ER. Thus, we have prepared a series of p-hydroxyphenyl-substituted CpRe(CO)(3) complexes and evaluated them (and, in some cases, their cyclopentadiene precursors) for binding to ER. These compounds constitute a new class of structurally integrated organometallic ligands for ER in which the CpMet(CO)(3 )organometallic unit forms the very structural core of these molecules and thus is necessarily intimately involved in their interaction with the receptor. The CpRe(CO)(3) compounds were prepared by reaction of the lithium salt of the arene-substituted cyclopentadiene with a suitable Re(CO)(3)(+) precursor, followed by deprotection of the methyl ether. The X-ray crystal structure of one of these analogues shows that it has the classical 'piano stool'-like geometry, with the alkyl groups directed upward, away from the tripodyl metal carbonyl base. The aryl-substituted CpRe(CO)(3) complexes that we have prepared all bind to the ER, some with affinity as great as 20% that of the native ligand, estradiol. In general, at least two p-hydroxyphenyl substituents and one to two alkyl groups attached to the organometallic cyclopentadienyl core are needed for high ER affinity. Where we have been able to make comparisons, the metal complexes bind to ER with an affinity greater than their cyclopentadiene precursors. The high affinity of some of these complexes indicates that the bulky Re(CO)(3) unit is able to exploit the considerable volume in the center of the ER ligand binding pocket that is not occupied by most ligands, a consideration that is supported by molecular modeling. The preparation of the best of these agents in technetium-99m labeled form is currently being investigated.


Subject(s)
Organometallic Compounds/chemical synthesis , Receptors, Estrogen/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/diagnostic imaging , Estrogens/chemistry , Female , Humans , Ligands , Models, Molecular , Organometallic Compounds/chemistry , Protein Binding , Radioisotopes/chemistry , Radioligand Assay , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Rhenium/chemistry , Structure-Activity Relationship
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