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1.
Eur Arch Paediatr Dent ; 25(1): 127-135, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38300412

RESUMO

PURPOSE: The internet is increasingly used to seek health information. A dental condition of increasing concern and public interest is molar incisor hypomineralisation (MIH), why we evaluated the information quality of German dentists 'websites on the topic of MIH. METHODS: A systematic search was performed by two independent investigators using three search engines. The information content of websites on MIH and technical, functional aspects, overall quality, and risk of bias were assessed using validated instruments (LIDA, DISCERN). Practice-related characteristics (practice type, specialization, setting, number and mean age of dentists) were recorded, and associations of these characteristics with websites' overall quality were explored using multivariable linear regression modelling. RESULTS: 70 sites were included. 52% were multipractices in urban areas (49%). The most common age group was middle-aged individuals (41-50 years). The average number of dentists/practice was 2.5. The majority met more than 50% of the DISCERN and LIDA criteria (90%, 91%). The MIH definition was frequently used (67%), MIH symptoms were described (64%), and 58% mentioned therapies. The prevalence of MIH was mentioned less frequently (48%). MIH example photographs were rarely shown (14%). In multivariable analysis, most practice-related factors were not significant for overall site quality. Only chain practices had slightly higher quality in this regard (2.2; 95% CI of 0.3-4.1). CONCLUSIONS: MIH is mentioned on a large proportion of dentists' websites. Overall technical, functional, and generic quality was high. Risk of bias is limited. While most websites provided a basic definition of MIH and its symptoms, important information for patients was missing.


Assuntos
Acetatos , Hipoplasia do Esmalte Dentário , Hipomineralização Molar , Pessoa de Meia-Idade , Humanos , Adulto , Odontólogos , Hipoplasia do Esmalte Dentário/epidemiologia , Dente Molar , Alemanha , Prevalência , Acetanilidas
2.
Antimicrob Agents Chemother ; 67(3): e0142622, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36744891

RESUMO

Moxifloxacin is included in some treatment regimens for drug-sensitive tuberculosis (TB) and multidrug-resistant TB (MDR-TB). Aiming to optimize dosing, we described moxifloxacin pharmacokinetic and MIC distribution in participants with MDR-TB. Participants enrolled at two TB hospitals in South Africa underwent intensive pharmacokinetic sampling approximately 1 to 6 weeks after treatment initiation. Plasma drug concentrations and clinical data were analyzed using nonlinear mixed-effects modeling with simulations to evaluate doses for different scenarios. We enrolled 131 participants (54 females), with median age of 35.7 (interquartile range, 28.5 to 43.5) years, median weight of 47 (42.0 to 54.0) kg, and median fat-free mass of 40.1 (32.3 to 44.7) kg; 79 were HIV positive, 29 of whom were on efavirenz-based antiretroviral therapy. Moxifloxacin pharmacokinetics were described with a 2-compartment model, transit absorption, and elimination via a liver compartment. We included allometry based on fat-free mass to estimate disposition parameters. We estimated an oral clearance for a typical patient to be 17.6 L/h. Participants treated with efavirenz had increased clearance, resulting in a 44% reduction in moxifloxacin exposure. Simulations predicted that, even at a median MIC of 0.25 (0.06 to 16) mg/L, the standard daily dose of 400 mg has a low probability of attaining the ratio of the area under the unbound concentration-time curve from 0 to 24 h to the MIC (fAUC0-24)/MIC target of >53, particularly in heavier participants. The high-dose WHO regimen (600 to 800 mg) yielded higher, more balanced exposures across the weight ranges, with better target attainment. When coadministered with efavirenz, moxifloxacin doses of up to 1,000 mg are needed to match these exposures. The safety of higher moxifloxacin doses in clinical settings should be confirmed.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Feminino , Humanos , Adulto , Moxifloxacina/uso terapêutico , Antituberculosos/farmacocinética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Alcinos/uso terapêutico
3.
S Afr Med J ; 111(10): 995-997, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34949296

RESUMO

BACKGROUND: Reports have emerged globally of antimicrobial resistance (AMR) in Neisseria gonorrhoeae and Mycoplasma genitalium infections. In South Africa (SA), there are substantial differences between private and public healthcare with regard to antimicrobial drug prescribing practice, which could affect AMR patterns of private and public healthcare patients. OBJECTIVES: To perform a pilot study to determine the frequency of AMR of N. gonorrhoeae and M. genitalium in patients accessing SA's private healthcare sector. METHODS: In this cross-sectional study, N. gonorrhoeae-positive cultures and M. genitalium DNA samples were collected from a private healthcare reference laboratory from August 2018 to August 2019. In N. gonorrhoeae-positive cultures, antimicrobial susceptibility testing was performed, followed by N. gonorrhoeae multiantigen sequence typing (NG-MAST) to determine genetic relatedness of the isolates. To determine macrolide and fluoroquinolone resistance rates, M. genitalium-positive samples were analysed by sequencing the 23S rRNA, gyrA and parC genes. RESULTS: Twenty-one N. gonorrhoeae- and 27 M. genitalium-positive specimens were included in this analysis. High rates of resistance were detected among gonococcal isolates, with 90% resistance to tetracycline, 86% to penicillin and 62% to ciprofloxacin, but no resistance to azithromycin, cefixime and ceftriaxone. NG-MAST revealed genetically diverse isolates with 83% novel NG-MAST sequence types. Macrolide and fluoroquinolone resistance-associated mutations were detected in 18.5% (n=5/27) and 7.4% (n=2/27) of M. genitalium strains, respectively. CONCLUSIONS: We observed high frequencies of ciprofloxacin, penicillin and tetracycline resistance in N. gonorrhoeae and macrolide resistance-associated mutations in M. genitalium in private healthcare sector patients in SA. This finding highlights the need to use diagnostics for sexually transmitted infections and to include the private healthcare sector in antimicrobial surveillance and stewardship programmes.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Neisseria gonorrhoeae/efeitos dos fármacos , Estudos Transversais , Feminino , Gonorreia/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Projetos Piloto , Setor Privado , África do Sul
4.
Sci Rep ; 11(1): 19758, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611216

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of exacerbations triggered by infections. The aim of this study was to determine the composition of the lung microbiome and lung virome in patients with COPD in an African setting and to compare their composition between the stable and exacerbated states. Twenty-four adult COPD patients were recruited from three hospitals. Sputum was collected and bacterial DNA was extracted. Targeted metagenomics was performed to determine the microbiome composition. Viral DNA and RNA were extracted from selected samples followed by cDNA conversion. Shotgun metagenomics sequencing was performed on pooled DNA and RNA. The most abundant phyla across all samples were Firmicutes and Proteobacteria. The following genera were most prevalent: Haemophilus and Streptococcus. There were no considerable differences for alpha and beta diversity measures between the disease states. However, a difference in the abundances between disease states was observed for: (i) Serratia (3% lower abundance in exacerbated state), (ii) Granulicatella (2.2% higher abundance in exacerbated state), (iii) Haemophilus (5.7% higher abundance in exacerbated state) and (iv) Veillonella (2.5% higher abundance in exacerbated state). Virome analysis showed a high abundance of the BeAn 58058 virus, a member of the Poxviridae family, in all six samples (90% to 94%). This study is among the first to report lung microbiome composition in COPD patients from Africa. In this small sample set, no differences in alpha or beta diversity between stable and exacerbated disease state was observed, but an unexpectedly high frequency of BeAn 58058 virus was observed. These observations highlight the need for further research of the lung microbiome of COPD patients in African settings.


Assuntos
Pulmão/microbiologia , Microbiota , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Idoso , Biodiversidade , Progressão da Doença , Feminino , Humanos , Masculino , Metagenoma , Metagenômica , Pessoa de Meia-Idade , Fatores de Risco , África do Sul/epidemiologia , Escarro/microbiologia
5.
BMC Microbiol ; 21(1): 228, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407769

RESUMO

BACKGROUND: Targeted metagenomics and IS-Pro method are two of the many methods that have been used to study the microbiome. The two methods target different regions of the 16 S rRNA gene. The aim of this study was to compare targeted metagenomics and IS-Pro methods for the ability to discern the microbial composition of the lung microbiome of COPD patients. METHODS: Spontaneously expectorated sputum specimens were collected from COPD patients. Bacterial DNA was extracted and used for targeted metagenomics and IS-Pro method. The analysis was performed using QIIME2 (targeted metagenomics) and IS-Pro software (IS-Pro method). Additionally, a laboratory cost per isolate and time analysis was performed for each method. RESULTS: Statistically significant differences were observed in alpha diversity when targeted metagenomics and IS-Pro methods' data were compared using the Shannon diversity measure (p-value = 0.0006) but not with the Simpson diversity measure (p-value = 0.84). Distinct clusters with no overlap between the two technologies were observed for beta diversity. Targeted metagenomics had a lower relative abundance of phyla, such as the Proteobacteria, and higher relative abundance of phyla, such as Firmicutes when compared to the IS-Pro method. Haemophilus, Prevotella and Streptococcus were most prevalent genera across both methods. Targeted metagenomics classified 23 % (144/631) of OTUs to a species level, whereas IS-Pro method classified 86 % (55/64) of OTUs to a species level. However, unclassified OTUs accounted for a higher relative abundance when using the IS-Pro method (35 %) compared to targeted metagenomics (5 %). The two methods performed comparably in terms of cost and time; however, the IS-Pro method was more user-friendly. CONCLUSIONS: It is essential to understand the value of different methods for characterisation of the microbiome. Targeted metagenomics and IS-Pro methods showed differences in ability in identifying and characterising OTUs, diversity and microbial composition of the lung microbiome. The IS-Pro method might miss relevant species and could inflate the abundance of Proteobacteria. However, the IS-Pro kit identified most of the important lung pathogens, such as Burkholderia and Pseudomonas and may work in a more diagnostics-orientated setting. Both methods were comparable in terms of cost and time; however, the IS-Pro method was easier to use.


Assuntos
Pulmão/microbiologia , Metagenômica/métodos , Metagenômica/normas , Microbiota/genética , Software/normas , Idoso , Idoso de 80 Anos ou mais , DNA Bacteriano/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Escarro/microbiologia
6.
J Chem Phys ; 153(19): 194504, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33218233

RESUMO

High energy electron scattering of liquid water (H2O) at near-ambient temperature and pressure was performed in a transmission electron microscope (TEM) to determine the radial distribution of water, which provides information on intra- and intermolecular spatial correlations. A recently developed environmental liquid cell enables formation of a stable water layer, the thickness of which is readily controlled by pressure and flow rate adjustments of a humid air stream passing between two silicon nitride (Si3N4) membranes. The analysis of the scattering data is adapted from the x-ray methodology to account for multiple scattering in the H2O:Si3N4 sandwich layer. For the H2O layer, we obtain oxygen-oxygen (O-O) and oxygen-hydrogen (O-H) peaks at 2.84 Å and 1.83 Å, respectively, in good agreement with values in the literature. This demonstrates the potential of our approach toward future studies of water-based physics and chemistry in TEMs or electron probes of structural dynamics.

8.
Rev Med Liege ; 75(3): 151-153, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32157838

RESUMO

Angiotensin converting enzyme inhibitors (ACE-i) are the most common cause of bradykininin angioedema. These bradykinin-mediated angioedemas are sometimes confused with histamine-induced angioedema, which may cause a late diagnosis and hence poor initial management, deleterious to the patient. This report describes a patient with a bradykinin-mediated angioedema soon after the initiation of perindopril, with laryngeal involvement requiring orotracheal intubation in emergency. The diagnosis was confirmed later and the assay of the activity of the enzymes involved in the catabolism of kinins - aminopeptidase P (APP), carboxypeptidase N (CPN) and Angiotensin-Converting Enzyme (ACE) - demonstrated a decrease of activity of both APP and ACE. As the diagnosis was not made initially, the specific treatments - concentrate of C1 inhibitor or antagonist of the B2 receptor of bradykinin (Icatibant) - were not administered. Any angioedema occurring during a treatment with ACE-i should be considered as a bradykinin-mediated angioedema.


Les inhibiteurs de l'enzyme de conversion de l'angiotensine (IEC) sont la cause la plus fréquente d'angioedème bradykininique. Ceux-ci se confondent facilement avec l'angioedème histaminique, pouvant causer un retard diagnostique et donc une mauvaise prise en charge initiale, délétère pour le patient. Nous rapportons le cas d'un patient présentant un angioedème induit par le périndopril, avec une atteinte laryngée nécessitant une intubation orotrachéale en urgence. Le diagnostic a été posé a posteriori et le dosage des activités des enzymes du catabolisme des kinines - aminopeptidase P (APP), carboxypeptidase N (CPN) et enzyme de conversion de l'angiotensine (ECA) - a démontré une diminution des activités APP et ECA. Le diagnostic n'étant pas posé initialement, les traitements spécifiques - concentré de C1 inhibiteur ou antagoniste des récepteurs B2 de la bradykinine (Icatibant) - n'ont pas été administrés. Tout angioedème sous IEC doit être considéré comme un angioedème bradykininique.


Assuntos
Angioedema , Inibidores da Enzima Conversora de Angiotensina , Bradicinina , Angioedema/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Perindopril
9.
J Antimicrob Chemother ; 75(4): 896-902, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953941

RESUMO

INTRODUCTION: Klebsiella pneumoniae with OXA-48-like enzymes were introduced into Tshwane Tertiary Hospital (TTH) (Pretoria, South Africa) during September 2015, causing nosocomial outbreaks. METHODS: PCR methodologies and WGS were used to characterize K. pneumoniae with carbapenemases (n = 124) from TTH (July 2015-December 2016). RESULTS: PCR was used to track K. pneumoniae ST307 with OXA-181 among 60% of carbapenemase-positive isolates in different wards/units over time and showed the transmission of IncX3 plasmids to other K. pneumoniae clones. WGS identified different ST307 clades: 307_OXA181 (consisting of two lineages, A and B) with OXA-181 on IncX3 plasmids (named p72_X3_OXA181) and clade 307_VIM with VIM-1 on IncFII plasmids. Clade 307_OXA181 lineage B was responsible for the rapid increase and transmission of OXA-181 K. pneumoniae in various wards/units throughout TTH, while the numbers of clade 307_OXA181 lineage A and clade 307_VIM remained low. Separate outbreaks were due to K. pneumoniae ST17 and ST29 with p72_X3_OXA181 plasmids. CONCLUSIONS: The high-risk clone K. pneumoniae ST307 with OXA-181 rapidly spread to different wards/units despite infection and prevention measures. ST307 clades and lineages seemingly acted differently in outbreak situations. This study also highlighted the threat of promiscuous plasmids such as p72_X3_OXA181.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Proteínas de Bactérias/genética , Células Clonais , Atenção à Saúde , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Plasmídeos/genética , África do Sul , beta-Lactamases/genética
10.
Rom J Anaesth Intensive Care ; 27(2): 43-76, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34056133

RESUMO

The high number of patients infected with the SARS-CoV-2 virus requiring care for ARDS puts sedation in the critical care unit (CCU) to the edge. Depth of sedation has evolved over the last 40 years (no-sedation, deep sedation, daily emergence, minimal sedation, etc.). Most guidelines now recommend determining the depth of sedation and minimizing the use of benzodiazepines and opioids. The broader use of alpha-2 adrenergic agonists ('alpha-2 agonists') led to sedation regimens beginning at admission to the CCU that contrast with hypnotics+opioids ("conventional" sedation), with major consequences for cognition, ventilation and circulatory performance. The same doses of alpha-2 agonists used for 'cooperative' sedation (ataraxia, analgognosia) elicit no respiratory depression but modify the autonomic nervous system (cardiac parasympathetic activation, attenuation of excessive cardiac and vasomotor sympathetic activity). Alpha-2 agonists should be selected only in patients who benefit from their effects ('personalized' indications, as opposed to a 'one size fits all' approach). Then, titration to effect is required, especially in the setting of systemic hypotension and/or hypovolemia. Since no general guidelines exist for the use of alpha-2 agonists for CCU sedation, our clinical experience is summarized for the benefit of physicians in clinical situations in which a recommendation might never exist (refractory delirium tremens; unstable, hypovolemic, hypotensive patients, etc.). Because the physiology of alpha-2 receptors and the pharmacology of alpha-2 agonists lead to personalized indications, some details are offered. Since interactions between conventional sedatives and alpha-2 agonists have received little attention, these interactions are addressed. Within the existing guidelines for CCU sedation, this article could facilitate the use of alpha-2 agonists as effective and safe sedation while awaiting large, multicentre trials and more evidence-based medicine.

11.
Breast Cancer ; 27(3): 426-434, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31832891

RESUMO

PURPOSE: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. METHODS: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. RESULTS: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean 'Q-physical well-being' scores were reported by the surveillance group (81.78 [CI 76.99-86.57]) than the BPM group (76.96 [CI 73.16 - 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. CONCLUSIONS: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for 'Q-psychological well-being'. The difference in 'Q-physical well-being' was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/cirurgia , Tomada de Decisão Compartilhada , Mastectomia/métodos , Medidas de Resultados Relatados pelo Paciente , Gestão de Riscos/normas , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos
12.
Arch Virol ; 165(1): 21-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31624917

RESUMO

To obtain insight into the sequence diversity of strawberry latent ringspot virus (SLRSV), isolates from collections and diagnostic samples were sequenced by high-throughput sequencing. For five SLRSV isolates, the complete genome sequences were determined, and for 18 other isolates nearly complete genome sequences were determined. The sequence data were analysed in relation to sequences of SLRSV and related virus isolates available in the NCBI GenBank database. The genome sequences were annotated, and sequences of the protease-polymerase (Pro-Pol) region and coat proteins (CPs) (large and small CP together) were used for phylogenetic analysis. The amino acid sequences of the Pro-Pol region were very similar, whereas the nucleotide sequences of this region were more variable. The amino acid sequences of the CPs were less similar, which was corroborated by the results of a serological comparison performed using antisera raised against different isolates of SLRSV. Based on these results, we propose that SLRSV and related unassigned viruses be assigned to a new genus within the family Secoviridae, named "Stralarivirus". Based on the phylogenetic analysis, this genus should include at least three viruses, i.e., SLRSV-A, SLRSV-B and lychnis mottle virus. The newly generated sequence data provide a basis for designing molecular tests to screen for SLRSV.


Assuntos
Fragaria/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Secoviridae/classificação , Análise de Sequência de RNA/métodos , Proteínas do Capsídeo/genética , RNA Polimerases Dirigidas por DNA/genética , Variação Genética , Anotação de Sequência Molecular , Peptídeo Hidrolases/genética , Filogenia , Vírus de Plantas/classificação , Vírus de Plantas/genética , Vírus de Plantas/isolamento & purificação , RNA Viral/genética , Secoviridae/genética , Secoviridae/isolamento & purificação
13.
Hautarzt ; 70(12): 948-952, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31754739

RESUMO

Resorcinol is a frequently used hair dye, whose quantitative risk assessment (QRA) for hair color products is presented in this review as an example to assess its skin sensitization risk after topical application. Its purpose is to determine the maximum concentration that can be used without expecting skin sensitization to occur. The focus is to prevent the de novo development of a contact allergy. Epidemiological data which are provided via dermatological surveillance, e.g., by the IVDK (Information Network of Departments of Dermatology) in Germany, are an important source of information that help to assess the quality and the effectivity of the QRA.


Assuntos
Alérgenos , Dermatite Alérgica de Contato , Resorcinóis , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/prevenção & controle , Alemanha , Humanos , Testes do Emplastro , Resorcinóis/efeitos adversos , Medição de Risco , Pele
14.
J Clin Microbiol ; 57(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31366692

RESUMO

Colistin has become increasingly important in the treatment of multidrug-resistant Gram-negative bacteria. Resistance to colistin has emerged globally, necessitating the need for an accurate method to detect colistin resistance. The colistin NP test has shown promise as a rapid screening assay for colistin resistance. This study compared the performance of an in-house-prepared colistin NP test against broth microdilution (BMD) as the gold standard and against Etest (bioMérieux, Marcy l'Etoile, France) as an alternative method. A total of 215 stored Enterobacteriaceae isolates were evaluated, of which 159 were resistant and 56 susceptible to colistin by BMD. The categorical agreement of the colistin NP test with BMD was found to be 98.1%, compared to 87.9% for the Etest. One major error was detected with both the colistin NP test and the Etest. Three very major errors were detected with the colistin NP test compared to 25 with the Etest. This resulted in a major error rate of 1.8% for both the colistin NP test and the Etest and a very major error rate of 1.9% and 15.7% for the colistin NP test and the Etest, respectively. The colistin NP test compared satisfactorily to the BMD reference method in determining colistin susceptibility. The colistin NP test is a rapid, inexpensive screening method for colistin resistance, especially in resource-limited settings.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Humanos , Reprodutibilidade dos Testes
15.
Sci Rep ; 8(1): 12222, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111773

RESUMO

Cystic fibrosis (CF) is an inherited recessive disease that affects mucocillary clearance in the lung, allowing it to be colonised with bacteria such as Staphylococcus aureus. To survive in the CF lung S. aureus adapts both phenotypically and genotypically, through various mechanisms. In this study, multiple specimens were collected from the participants and were processed routinely and were additionally cultured in chromogenic media. Multiplex PCR assays were employed to detect methicillin resistance and selected virulence and quaternary ammonium compound (qac) genes. Genetic relatedness of the S. aureus was determined using agr, SCCmec and spa typing as well as pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Thirty-three S. aureus isolates were isolated, of which 51% (17/33) were methicillin resistant S. aureus (MRSA). The virulence and qac genes were more prevalent in MRSA than the methicillin sensitive S. aureus (MSSA) isolates. The PFGE analysis showed nine distinct pulsotypes while MLST showed eight sequence types. All the STs detected in this study, except for ST508 have been previously isolated from CF patients according to the literature. This study showed a genetically diverse S. aureus population with a high prevalence of virulence genes among the MRSA isolates from the CF clinic.


Assuntos
Fibrose Cística/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Adolescente , Adulto , Toxinas Bacterianas/genética , Criança , Pré-Escolar , Eletroforese em Gel de Campo Pulsado/métodos , Exotoxinas/genética , Feminino , Genótipo , Humanos , Lactente , Masculino , Resistência a Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus/métodos , África do Sul , Infecções Estafilocócicas/microbiologia , Centros de Atenção Terciária , Fatores de Virulência/genética
18.
PLoS One ; 12(9): e0183855, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28949967

RESUMO

PURPOSE: To establish a preoperative decision model for accurate indication of systemic therapy in early-stage breast cancer using multiparametric MRI at 7-tesla field strength. MATERIALS AND METHODS: Patients eligible for breast-conserving therapy were consecutively included. Patients underwent conventional diagnostic workup and one preoperative multiparametric 7-tesla breast MRI. The postoperative (gold standard) indication for systemic therapy was established from resected tumor and lymph-node tissue, based on 10-year risk-estimates of breast cancer mortality and relapse using Adjuvant! Online. Preoperative indication was estimated using similar guidelines, but from conventional diagnostic workup. Agreement was established between preoperative and postoperative indication, and MRI-characteristics used to improve agreement. MRI-characteristics included phospomonoester/phosphodiester (PME/PDE) ratio on 31-phosphorus spectroscopy (31P-MRS), apparent diffusion coefficients on diffusion-weighted imaging, and tumor size on dynamic contrast-enhanced (DCE)-MRI. A decision model was built to estimate the postoperative indication from preoperatively available data. RESULTS: We included 46 women (age: 43-74yrs) with 48 invasive carcinomas. Postoperatively, 20 patients (43%) had positive, and 26 patients (57%) negative indication for systemic therapy. Using conventional workup, positive preoperative indication agreed excellently with positive postoperative indication (N = 8/8; 100%). Negative preoperative indication was correct in only 26/38 (68%) patients. However, 31P-MRS score (p = 0.030) and tumor size (p = 0.002) were associated with the postoperative indication. The decision model shows that negative indication is correct in 21/22 (96%) patients when exempting tumors larger than 2.0cm on DCE-MRI or with PME>PDE ratios at 31P-MRS. CONCLUSIONS: Preoperatively, positive indication for systemic therapy is highly accurate. Negative indication is highly accurate (96%) for tumors sized ≤2,0cm on DCE-MRI and with PME≤PDE ratios on 31P-MRS.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Período Pré-Operatório
19.
CPT Pharmacometrics Syst Pharmacol ; 6(7): 430-438, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28597978

RESUMO

Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed-effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3-fold for sulfadoxine but decreased by 18% for pyrimethamine. Postpartum sulfadoxine clearance decreased gradually over 13 weeks. This finding, together with hematocrit-based scaling of plasma to whole-blood concentrations and allometric scaling of pharmacokinetics parameters with body weight, enabled site-specific differences in the pharmacokinetic profiles to be reduced significantly but not eliminated. Further research is necessary to explain residual site-specific differences and elucidate whether dose-optimization, to address the 3-fold increase in clearance of sulfadoxine in pregnant women, is necessary, viable, and safe with the current fixed dose combination of sulfadoxine/pyrimethamine.


Assuntos
Antimaláricos/farmacocinética , Modelos Biológicos , Pirimetamina/farmacocinética , Sulfadoxina/farmacocinética , Adulto , África , Antimaláricos/sangue , Antimaláricos/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Malária/prevenção & controle , Período Pós-Parto/sangue , Período Pós-Parto/metabolismo , Gravidez/sangue , Gravidez/metabolismo , Pirimetamina/sangue , Pirimetamina/uso terapêutico , Sulfadoxina/sangue , Sulfadoxina/uso terapêutico , Adulto Jovem
20.
Case Rep Crit Care ; 2017: 6263578, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28299209

RESUMO

There is a paucity of information concerning cardiac tumours of the pulmonary valve due to their rarity at this location. We report a case of a 47-year-old patient suffering from haemoptysis, asthenia, and acute kidney injury (AKI). A transthoracic echocardiography (TTE) revealed a mass on the pulmonary valve. Further diagnostic investigation was completed until he exhibited worsening hemodynamic instability. This case emphasizes the lack of information regarding the management of a pulmonary valve tumour.

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