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1.
J Clin Tuberc Other Mycobact Dis ; 32: 100381, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37323244

RESUMO

Medical tourism is becoming increasingly popular. The most popularly sought operations are cosmetic procedures. With the increase in cosmetic tourism, it is unsurprising that there has also been a rise in skin and soft tissue infections caused by nontuberculous mycobacteria (NTM); in particular by the rapidly growing mycobacteria species. Here we provide a case of a 35 year-old woman who presented after autologous fat grafting with multiple painful, violaceous, and purulent nodules on her arms, legs, and breasts. Infection was found to be due to Mycobacterium abscessus. She was successfully treated with azithromycin, clofazimine, rifabutin, amikacin, imipenem-cilastatin-relebactam (Recarbrio™) and imipenem-cilastatin. This is the first described case of a M. abscessus infection successfully treated using this combination.

2.
Int J STD AIDS ; 34(7): 434-438, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36920941

RESUMO

INTRODUCTION: During spring 2022, an outbreak of Monkeypox (mpox) emerged as an infection of concern in Europe. Due to the overlapping clinical features of mpox and bacterial infections, diagnosis of concomitant bacterial infection is challenging. In this prospective cohort study, we report the incidence, severity, and progression of patients with secondary bacterial infection complicating mpox infection. METHOD: Data were collected via a bespoke mpox telemedicine service provided by Infection services at North Manchester General Hospital, UK. A diagnosis of secondary bacterial infection was based on the history (balanitis, surrounding erythema, purulent discharge and nasal ulceration) and review of patient-collected medical photography. Patient were reviewed face-to-face where necessary. RESULTS: Secondary bacterial infection was diagnosed in 15 of 129 (11.6%) patients with mpox. Three patients with secondary bacterial infection (3/129, 2.3%) required admission to hospital and one patient underwent surgical debridement. Median healing (thus, isolation) times were longer in those with bacterial infection. DISCUSSION: In this prospective cohort study of patients with mpox, secondary bacterial infection was infrequent and predominantly mild. The virtual ward and telemedicine follow up allowed for the prompt recognition of secondary bacterial infections and timely antibiotic administration. Due to concerns regarding nosocomial transmission, mild clinical course and limited inpatient bed capacity, we believe this model of outpatient management for mpox (Clade II B.1 lineage) could be replicated in other low risk populations where suitable home isolation facilities exist.


Assuntos
Infecções Bacterianas , Coinfecção , Mpox , Masculino , Humanos , Estudos Prospectivos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Hospitais Gerais
4.
Mol Pharmacol ; 94(3): 1079-1091, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29980659

RESUMO

Vasoconstrictor-driven G protein-coupled receptor (GPCR)/phospholipase C (PLC) signaling increases intracellular Ca2+ concentration to mediate arterial contraction. To counteract vasoconstrictor-induced contraction, GPCR/PLC signaling can be desensitized by G protein-coupled receptor kinases (GRKs), with GRK2 playing a predominant role in isolated arterial smooth muscle cells. In this study, we use an array of GRK2 inhibitors to assess their effects on the desensitization of UTP and angiotensin II (AngII)-mediated arterial contractions. The effects of GRK2 inhibitors on the desensitization of UTP- or AngII-stimulated mesenteric third-order arterial contractions, and PLC activity in isolated mesenteric smooth muscle cells (MSMC), were determined using wire myography and Ca2+ imaging, respectively. Applying a stimulation protocol to cause receptor desensitization resulted in reductions in UTP- and AngII-stimulated arterial contractions. Preincubation with the GRK2 inhibitor paroxetine almost completely prevented desensitization of UTP- and attenuated desensitization of AngII-stimulated arterial contractions. In contrast, fluoxetine was ineffective. Preincubation with alternative GRK2 inhibitors (Takeda compound 101 or CCG224063) also attenuated the desensitization of UTP-mediated arterial contractile responses. In isolated MSMC, paroxetine, Takeda compound 101, and CCG224063 also attenuated the desensitization of UTP- and AngII-stimulated increases in Ca2+, whereas fluoxetine did not. In human uterine smooth muscle cells, paroxetine reversed GRK2-mediated histamine H1 receptor desensitization, but not GRK6-mediated oxytocin receptor desensitization. Utilizing various small-molecule GRK2 inhibitors, we confirm that GRK2 plays a central role in regulating vasoconstrictor-mediated arterial tone, highlighting a potentially novel strategy for blood pressure regulation through targeting GRK2 function.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Quinase 2 de Receptor Acoplado a Proteína G/fisiologia , Músculo Liso Vascular/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Animais , Linhagem Celular Transformada , Relação Dose-Resposta a Droga , Humanos , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos
5.
Hypertension ; 70(5): 1042-1048, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28847892

RESUMO

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.


Assuntos
Anti-Hipertensivos , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Hipertensão , Adesão à Medicação/psicologia , Conduta do Tratamento Medicamentoso/normas , Adulto , Idoso , Anti-Hipertensivos/análise , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Biomarcadores/urina , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/psicologia , Cromatografia Líquida/métodos , República Tcheca/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Melhoria de Qualidade , Reino Unido/epidemiologia
6.
Ann Clin Biochem ; 53(6): 702-705, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27099337

RESUMO

Background The measurement of cardiac troponin is central for the diagnosis of myocardial infarction (MI). It is recommended that a coefficient of variation of ≤10% is achieved at the diagnostic threshold and significant change between serial measurements reported. Many modern laboratories use multiple analysers linked by automation where samples are randomly assigned to an analyser. It is therefore important to consider the combined effect of all analysers on the analytical performance of troponin measurement. Method The performance of a contemporary troponin-I (cTn-I) assay run on three analysers, linked by an automated track, was undertaken across a range of cTn-I concentrations. The data for the three analysers were aggregated to obtain the combined analytical coefficient of variation (CVA) and reference change values (RCVs). Results The CVA improved with increasing concentration and calculated RCVs ranged from 67.2% (±13 ng/L) to 32% (±160 ng/L) between cTn-I values 20 ng/L and 500 ng/L. Although there were significant differences in cTn-I measurement between analysers around the diagnostic threshold ( P < 0.05), the CVA was 13.6%. Conclusions We demonstrate that there are significant differences between the performances of analysers which can impact the biochemical criteria for the diagnosis of MI. We also show that the RCV varies according to baseline cTn-I values and that reporting a single RCV across the analytical range of cTn-I may not be appropriate.


Assuntos
Automação Laboratorial/normas , Bioensaio/normas , Infarto do Miocárdio/diagnóstico , Troponina T/sangue , Biomarcadores/sangue , Humanos , Infarto do Miocárdio/sangue , Miocárdio/metabolismo , Miocárdio/patologia , Variações Dependentes do Observador , Valores de Referência
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