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1.
Antimicrob Agents Chemother ; 67(12): e0013623, 2023 12 14.
Article in English | MEDLINE | ID: mdl-37966229

ABSTRACT

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced ß-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal ß-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥105 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE (P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE (P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.


Subject(s)
Cystic Fibrosis , Staphylococcal Infections , Adult , Humans , Adolescent , Methicillin/pharmacology , Methicillin/therapeutic use , Cefazolin/pharmacology , Staphylococcus aureus/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Cystic Fibrosis/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Monobactams/pharmacology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Ceftazidime/pharmacology , beta Lactam Antibiotics , Microbial Sensitivity Tests
2.
Can Respir J ; 8(6): 439-42, 2001.
Article in English | MEDLINE | ID: mdl-11753458

ABSTRACT

The case of Munchausen's syndrome presenting as hemoptysis in a 12-year-old girl is presented. The features of Munchausen's syndrome are reviewed. Munchausen's syndrome should be included in the differential diagnosis of hemoptysis in a child, especially when accompanied by a dramatic presentation, changing symptoms and negative diagnostic investigations.


Subject(s)
Hemoptysis/diagnosis , Munchausen Syndrome/diagnosis , Child , Diagnosis, Differential , Female , Humans , Self-Injurious Behavior
3.
J Gend Specif Med ; 3(8): 57-61, 2000.
Article in English | MEDLINE | ID: mdl-11253268

ABSTRACT

Asthma is a common chronic disease that can have a significant impact on individuals' daily lives. It is characterized by wheeze, shortness of breath, chest tightness, and cough secondary to airway inflammation and hyperresponsiveness to a variety of stimuli. Asthma is far more common in boys than girls during early childhood. The prevalence equalizes between the genders during adolescence and then switches to a female predominance in adulthood. This article reviews the epidemiology and possible pathophysiologic mechanisms for the observed differences in asthma between the genders. In practical terms, the impact of asthma may be different according to gender in terms of daily activities for children and adolescents. The implications of gender differences in asthma for the health professional will also be discussed.


Subject(s)
Asthma/epidemiology , Asthma/physiopathology , Adolescent , Child , Chronic Disease , Female , Humans , Male , Prevalence , Sex Factors
4.
J Cell Physiol ; 110(2): 169-74, 1982 Feb.
Article in English | MEDLINE | ID: mdl-6279682

ABSTRACT

A growth-factor-like substance capable of inducing nontransformed mouse AKR-2B, rat NRK, and EGF-receptorless mouse NR6 cells to form progressively growing colonies in soft agar was identified in acid/ethanol extracts of 17-day mouse embryos. This "mouse embryo factor" (MEF) is similar to previously described transforming growth factors in that it is capable of stimulating DNA synthesis and conferring a reversible transformed morphology on nontransformed cells in vitro. Passage of crude embryo extracts over a Bio-Gel P-60 column gave a major peak of soft agar growth-stimulating activity in the 15,000 molecular weight range with a minor peak at about 22,000. This biological activity was sensitive to treatment with either trypsin or dithiothreitol, but was unaffected by heat (56 degrees C for 30 minutes or 100 degrees C for 3 minutes), indicating that the activity is due to a heat-stable polypeptide(s) with disulfide bonds. Separation of these polypeptide(s) by chromatography on carboxymethyl cellulose revealed two peaks of soft agar growth-stimulating activity which did not cochromatograph with a peak of epidermal growth factor receptor-competing activity. The similarities of this mouse embryo-derived growth factor to previously identified transforming growth factors suggest that both fetal development and neoplastic transformation may be affected by similar mechanisms.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Growth Substances/isolation & purification , Mice, Inbred Strains/embryology , Animals , Binding, Competitive , Cell Division , Chromatography, Gel , Chromatography, Ion Exchange , DNA/biosynthesis , Dithiothreitol/pharmacology , ErbB Receptors , Fibroblasts/metabolism , Hot Temperature , Humans , Mice , Rats , Receptors, Cell Surface/metabolism , Trypsin/pharmacology
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