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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.
Eur J Clin Microbiol Infect Dis ; 37(7): 1345-1352, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29728782

ABSTRACT

Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24 months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5-8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6-9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.


Subject(s)
Antiviral Agents/therapeutic use , Cystic Fibrosis/pathology , Palivizumab/therapeutic use , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus, Human/drug effects , Canada/epidemiology , Child, Preschool , Female , Heart Defects, Congenital , Humans , Infant , Male , Prospective Studies , Registries , Respiratory Syncytial Virus Infections/drug therapy
3.
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
4.
Nat Neurosci ; 3(10): 986-91, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11017170

ABSTRACT

Distinct cell lineages established early in development are usually maintained throughout adulthood. Thus, adult stem cells have been thought to generate differentiated cells specific to the tissue in which they reside. This view has been challenged; for example, neural stem cells can generate cells that normally originate from a different germ layer. Here we show that acutely isolated and clonally derived neural stem cells from mice and humans could produce skeletal myotubes in vitro and in vivo, the latter following transplantation into adult animals. Myogenic conversion in vitro required direct exposure to myoblasts, and was blocked if neural cells were clustered. Thus, a community effect between neural cells may override such myogenic induction. We conclude that neural stem cells, which generate neurons, glia and blood cells, can also produce skeletal muscle cells, and can undergo various patterns of differentiation depending on exposure to appropriate epigenetic signals in mature tissues.


Subject(s)
Brain Tissue Transplantation/methods , Cell Differentiation/physiology , Cell Lineage/physiology , Central Nervous System/embryology , Muscle, Skeletal/embryology , Stem Cell Transplantation , Stem Cells/metabolism , Age Factors , Animals , Cell Communication/physiology , Cell Culture Techniques/methods , Central Nervous System/metabolism , Central Nervous System/ultrastructure , Coculture Techniques , Humans , Mice , Mice, Transgenic , Muscle, Skeletal/metabolism , Muscle, Skeletal/ultrastructure , Stem Cells/ultrastructure
5.
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
6.
Pediatr Infect Dis J ; 18(12): 1078-80, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10608628

ABSTRACT

BACKGROUND: In an era of increasing antibiotic resistance, the prevalence of antibiotic usage and associated factors should be ascertained to optimize their use. We set out to determine the prevalence of antibiotic use in febrile children diagnosed with respiratory tract illnesses at a children's hospital emergency department; to determine how often viral studies were conducted; and to identify patient characteristics associated with antibiotic use. METHODS: We conducted a retrospective study of antibiotic use in febrile children 3 months to 10 years old presenting with respiratory illnesses during two 1-month periods. Patient charts and laboratory tests were reviewed. Antibiotic use was related to diagnosis by logistic regression. RESULTS: A total of 836 patient visits were selected. Antibiotics were prescribed for otitis media in 96% of patients, for pneumonia in 100%, for pharyngitis in 66%, for bronchiolitis in 38%, for reactive airway disease in 24% and for viral or "upper respiratory tract illness" in 14%. For viral illness or upper respiratory tract infection, antibiotic use was associated with a fever duration of >48 h [odds ratio (OR), 3.2; 95% confidence interval (CI) 1.7, 5.9] and having a chest radiograph performed (OR 2.1; 95% CI 1.02, 4.37). Patients with pharyngitis who had a throat swab were less likely to receive an antibiotic (OR 0.08; 95% CI 0.02, 0.4) than those who did not have a swab. In this emergency department antibiotic use for these indications decreased by 11% during the 1997 to 1998 study interval (P < 0.001). CONCLUSION: Antibiotics were commonly prescribed for pharyngitis, bronchiolitis and reactive airway disease, which are conditions principally caused by viruses. Addressing reasons why there is a difference between guidelines and antibiotic use in these conditions may be important.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Emergency Service, Hospital/statistics & numerical data , Fever/therapy , Hospitals, Pediatric/statistics & numerical data , Respiratory Tract Diseases/therapy , Canada , Child , Child, Preschool , Drug Utilization , Female , Fever/complications , Fever/microbiology , Humans , Infant , Logistic Models , Male , Respiratory Tract Diseases/complications , Respiratory Tract Diseases/microbiology , Retrospective Studies , Virus Diseases/diagnosis
7.
J Neurosci ; 19(9): 3287-97, 1999 May 01.
Article in English | MEDLINE | ID: mdl-10212288

ABSTRACT

The subventricular zone (SVZ) of the adult mammalian forebrain contains kinetically distinct precursor populations that contribute new neurons to the olfactory bulb. Because among forebrain precursors there are stem-like cells that can be cultured in the presence of mitogens such as epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), we asked whether distinct subsets of stem-like cells coexist within the SVZ or whether the proliferation of a single type of SVZ stem-like cell is controlled by several GFs. We show that the latter is the case. Thus cells isolated from the SVZ coexpress the EGF and FGF receptors; by quantitative analysis, the number of stem-like cells isolated from the SVZ by either FGF2 or EGF is the same, whereas no additive effect occurs when these factors are used together. Furthermore, short-term administration of high-dose [3H]thymidine in vivo depletes both the EGF- and FGF2-responsive stem-like cell populations equally, showing they possess closely similar proliferation kinetics and likely belong to the constitutively proliferating SVZ compartment. By subcloning and population analysis, we demonstrate that responsiveness to more than one GF endows SVZ cells with an essential stem cell feature, the ability to vary self-renewal, that was until now undocumented in CNS stem-like cells. The multipotent stem cell-like population that expands slowly in the presence of FGF2 in culture switches to a faster growth mode when exposed to EGF alone and expands even faster when exposed to both GFs together. Analogous responses are observed when the GFs are used in the reverse order, and furthermore, these growth rate modifications are fully reversible.


Subject(s)
Epidermal Growth Factor/pharmacology , ErbB Receptors/genetics , Fibroblast Growth Factor 2/pharmacology , Neurons/cytology , Neurons/physiology , Prosencephalon/cytology , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Fibroblast Growth Factor/genetics , Stem Cells/cytology , Animals , Cell Differentiation , Cell Division/drug effects , Cells, Cultured , Corpus Striatum/cytology , Corpus Striatum/physiology , Epidermal Growth Factor/physiology , ErbB Receptors/physiology , Fibroblast Growth Factor 2/physiology , Kinetics , Mice , Neurons/drug effects , Prosencephalon/physiology , Receptor Protein-Tyrosine Kinases/physiology , Receptor, Fibroblast Growth Factor, Type 1 , Receptors, Fibroblast Growth Factor/physiology , Reverse Transcriptase Polymerase Chain Reaction , Stem Cells/drug effects , Stem Cells/physiology
8.
Science ; 283(5401): 534-7, 1999 Jan 22.
Article in English | MEDLINE | ID: mdl-9915700

ABSTRACT

Stem cells are found in various organs where they participate in tissue homeostasis by replacing differentiated cells lost to physiological turnover or injury. An investigation was performed to determine whether stem cells are restricted to produce specific cell types, namely, those from the tissue in which they reside. After transplantation into irradiated hosts, genetically labeled neural stem cells were found to produce a variety of blood cell types including myeloid and lymphoid cells as well as early hematopoietic cells. Thus, neural stem cells appear to have a wider differentiation potential than previously thought.


Subject(s)
Blood Cells/cytology , Hematopoietic Stem Cells/cytology , Prosencephalon/cytology , Stem Cells/cytology , Animals , Blood Cells/immunology , Bone Marrow Cells/immunology , Cell Differentiation , Cells, Cultured , Colony-Forming Units Assay , Female , H-2 Antigens/analysis , Hematopoiesis , Lac Operon , Lymphocytes/cytology , Lymphocytes/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , Prosencephalon/embryology , Spleen/cytology , Stem Cell Transplantation , Stem Cells/immunology
9.
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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