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1.
Open Forum Infect Dis ; 7(1): ofz499, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32016130

RESUMO

Francisella tularensis has a low infectious dose and can infect laboratory staff handling clinical specimens. The risk to health care providers exposed during patient care is poorly defined. We describe 9 examples of health care providers who did not develop tularemia after significant exposures to infected patients.

2.
JAMA Neurol ; 70(8): 1060-4, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23732875

RESUMO

IMPORTANCE: The Jarisch-Herxheimer reaction (JHR) is a well-recognized transient worsening of signs and symptoms occurring soon after the first dose of an appropriate antibiotic for several spirochetal infections. The pathogenesis of this reaction is poorly understood. In this case study of cerebrospinal fluid (CSF) cytokines, we aimed to improve understanding of the pathogenesis of JHR in patients with neurosyphilis who develop transient neurologic signs. OBSERVATIONS: Four hours after receiving penicillin for general paresis, a 55-year-old man developed a severe JHR characterized by fever, tachycardia, hypertension, obtundation, seizures, and a neutrophilia lasting 18 hours. Cerebrospinal fluid obtained at the peak of the JHR demonstrated a switch from a mild lymphophilia to a moderate neutrophilia. He had markedly elevated CSF interleukin (IL) 8 and likely elevated IL-1ß, IL-10, and IL-15 levels, which returned to normal in follow-up CSF examination results. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of elevated CSF cytokines in a patient with a JHR, which possibly contributed to the neurologic signs of JHR. Further studies on the innate inflammatory response during episodes of acute infection and inflammation are needed to develop targeted therapies to modulate this system, which could, in turn, improve future outcomes and modify the JHR.


Assuntos
Citocinas/biossíntese , Citocinas/líquido cefalorraquidiano , Neurossífilis/tratamento farmacológico , Penicilinas/efeitos adversos , Antibacterianos/efeitos adversos , Febre/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Neurossífilis/complicações , Neurossífilis/etiologia , Taquicardia/induzido quimicamente , Resultado do Tratamento , Treponema pallidum/efeitos dos fármacos , Treponema pallidum/patogenicidade
3.
Virology ; 433(1): 262-72, 2012 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-22939285

RESUMO

West Nile virus (WNV) is an arthropod-borne virus with a worldwide distribution that causes neurologic disease and death. Autophagy is a cellular homeostatic mechanism involved in antiviral responses but can be subverted to support viral growth as well. We show that autophagy is induced by WNV infection in cell culture and in primary neuron cultures. Following WNV infection, lysosomes co-localize with autophagosomes resulting in LC3B-II turnover and autolysosomal acidification. However, activation or inhibition of autophagy has no significant effect on WNV growth but pharmacologic inhibition of PI3 kinases associated with autophagy reduce WNV growth. Basal levels of p62/sequestosome1(SQSTM1) do not significantly change following WNV-induced autophagy activation, but p62 is turned over or degraded by autophagy activation implying that p62 expression is increased following WNV-infection. These data show that WNV-induces autophagy but viral growth is independent of autophagy activation suggesting that WNV-specific interactions with autophagy have diverged from other flaviviruses.


Assuntos
Autofagia , Neurônios/virologia , Fagossomos/virologia , Replicação Viral/fisiologia , Vírus do Nilo Ocidental/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Chlorocebus aethiops , Cricetinae , Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/metabolismo , Fagossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Cultura Primária de Células , Inibidores de Proteínas Quinases/farmacologia , Proteólise , Células Vero
5.
J Med Toxicol ; 6(2): 160-4, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20358411

RESUMO

More than 2 million Americans use cocaine each month (National Survey on Drug Use and Health, Department of Health and Human Services: Substance Abuse and Mental Health Services Administration (SAMHSA) & Office of Applied Studies (OAS), Rockville, MD 2007). Starting in early 2003, South American cocaine cartels began to add levamisole, a pharmaceutical agent, to bulk cocaine prior to shipment to the USA (Valentino and Fuentecilla 2005). A dramatic increase in the prevalence of levamisole in cocaine was noted in early 2008. By October, 30% of cocaine bricks analyzed by the United States Drug Enforcement Administration contained levamisole (Casale et al. 2008). Exposure to levamisole can cause agranulocytosis (Amery and Bruynseels 1992). We report the first confirmed case of agranulocytosis associated with consumption of levamisole-contaminated cocaine in the USA. A previously healthy adult male presented to the emergency department with 5 days of mouth pain. He admitted to chronic active ethanol and crack cocaine abuse. Laboratory studies revealed severe neutropenia, with an absolute neutrophil count of 19 cells/mm³ (normal = 1,500-8,000 cells/mm³). A urine screen for drugs of abuse was positive for cocaine metabolites and opiates. Evaluation of a peripheral blood smear showed leukopenia with severe absolute neutropenia. A bone marrow biopsy revealed recently injured bone marrow showing early recovery. While in the hospital, the patient had little spontaneous bone marrow recovery. He received granulocyte colony-stimulating factor with improvement in peripheral white blood cell counts. The residue in the patient's crack pipe contained 10% levamisole. Subsequently, levamisole was detected in the patient's urine. Levamisole-associated agranulocytosis should be considered in the diagnosis of patients who present with neutropenia and a history or evidence of cocaine use.


Assuntos
Agranulocitose/induzido quimicamente , Cocaína/intoxicação , Levamisol/intoxicação , Adulto , Agranulocitose/sangue , Agranulocitose/patologia , Medula Óssea/patologia , Cocaína Crack/intoxicação , Contaminação de Medicamentos , Humanos , Contagem de Leucócitos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Masculino , Neutropenia/sangue , Neutropenia/induzido quimicamente
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