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1.
Radiology ; 311(1): e231348, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38625010

RESUMO

The diagnosis and management of chronic nonspinal osteomyelitis can be challenging, and guidelines regarding the appropriateness of performing percutaneous image-guided biopsies to acquire bone samples for microbiological analysis remain limited. An expert panel convened by the Society of Academic Bone Radiologists developed and endorsed consensus statements on the various indications for percutaneous image-guided biopsies to standardize care and eliminate inconsistencies across institutions. The issued statements pertain to several commonly encountered clinical presentations of chronic osteomyelitis and were supported by a literature review. For most patients, MRI can help guide management and effectively rule out osteomyelitis when performed soon after presentation. Additionally, in the appropriate clinical setting, open wounds such as sinus tracts and ulcers, as well as joint fluid aspirates, can be used for microbiological culture to determine the causative microorganism. If MRI findings are positive, surgery is not needed, and alternative sites for microbiological culture are not available, then percutaneous image-guided biopsies can be performed. The expert panel recommends that antibiotics be avoided or discontinued for an optimal period of 2 weeks prior to a biopsy whenever possible. Patients with extensive necrotic decubitus ulcers or other surgical emergencies should not undergo percutaneous image-guided biopsies but rather should be admitted for surgical debridement and intraoperative cultures. Multidisciplinary discussion and approach are crucial to ensure optimal diagnosis and care of patients diagnosed with chronic osteomyelitis.


Assuntos
Osteomielite , Adulto , Humanos , Biópsia por Agulha Fina , Osteomielite/diagnóstico por imagem , Osteomielite/terapia , Inflamação , Antibacterianos , Radiologistas
2.
Curr Opin Infect Dis ; 32(3): 265-271, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31021957

RESUMO

PURPOSE OF REVIEW: Spinal epidural abscess (SEA) is still a rare but potentially very morbid infection of the spine. In recent years, the incidence has risen sharply but the condition remains a medical conundrum wrought with unacceptably long diagnostic delays. The outcome depends on timely diagnosis and missed opportunities can be associated with catastrophic consequences. Management and outcomes have improved over the past decade. This review focuses on risk factors and markers that can aid in establishing the diagnosis, the radiological characteristics of SEA on MRI and their clinical implications, as well as the importance of establishing clear indications for surgical decompression. RECENT FINDINGS: This once exclusively surgically managed entity is increasingly treated conservatively with antimicrobial therapy. Patients diagnosed in a timely fashion, prior to cord involvement and the onset of neurologic deficits can safely be managed without decompressive surgery with targeted antimicrobial therapy. Patients with acute cord compression and gross neurologic deficits promptly undergo decompression. The greatest therapeutic dilemma remains the group with mild neurological deficits. As failure rates of delayed surgery approach 40%, recent research is focused on predictive models for failure of conservative SEA management. In addition, protocols are being implemented with some success, to shorten the diagnostic delay of SEA on initial presentation. SUMMARY: SEA is a potentially devastating condition that is frequently missed. Protocols are put in place to facilitate early evaluation of back pain in patients with red flags with appropriate cross-sectional imaging, namely contrast-enhanced MRI. Efforts for establishing clear-cut indications for surgical decompression of SEA are underway.


Assuntos
Antibacterianos/uso terapêutico , Descompressão Cirúrgica/métodos , Gerenciamento Clínico , Abscesso Epidural/diagnóstico por imagem , Abscesso Epidural/terapia , Imageamento por Ressonância Magnética/métodos , Regras de Decisão Clínica , Abscesso Epidural/epidemiologia , Humanos , Incidência , Fatores de Risco
3.
World Neurosurg ; 98: 870.e11-870.e15, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27993739

RESUMO

BACKGROUND: Septic arthritis of the atlantoaxial facet joint is extremely rare. Contiguous spread to the median atlantoaxial joints with subsequent dens erosion can lead to atlantoaxial instability. Misleading normal inflammatory markers can result in delayed diagnosis and catastrophic consequences. CASE DESCRIPTION: A 56-year-old man presented with right-sided neck pain that had lasted for 2 days. He did not have fever or chills, and his serum C-reactive protein and erythrocyte sedimentation rate were normal. The patient was diagnosed with acute neck strain and treated conservatively. The pain continued for the next 3 weeks; cervical spine radiographs demonstrated normal findings with the exception of degenerative changes. The patient was treated with physical rehabilitation for the presumed neck strain and degenerative changes of the cervical vertebrae. Worsening neck pain and stiffness prompted a magnetic resonance imaging study obtained 5 weeks after the initial presentation, which showed an epidural collection with septic arthritis of the right facet and median atlantoaxial joints. Computed tomography demonstrated severe dens erosion. Surgical evacuation of the abscess and occipitocervical fusion were performed. Pathologic evaluation of tissue obtained during surgery demonstrated the presence of an infection, and Streptococcus anginosus grew from cultures. CONCLUSIONS: Infection must be considered in the differential diagnosis for neck pain when imaging findings are suggestive of an infectious process, even in an afebrile patient with normal C-reactive protein and erythrocyte sedimentation rate levels. Magnetic resonance imaging and computed tomography can play a critical role in such cases, potentially leading to a more timely diagnosis.


Assuntos
Artrite Infecciosa/patologia , Articulação Atlantoaxial/patologia , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/microbiologia , Articulação Atlantoaxial/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fusão Vertebral/métodos , Infecções Estafilocócicas/complicações , Tomógrafos Computadorizados , Tomografia Computadorizada por Raios X
4.
Eur J Med Chem ; 102: 288-302, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26291038

RESUMO

Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and l-ascorbic acid (l-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of l-ascorbic (1-4, 8-10, 13-15) and imino-l-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of l-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 ± 1.8 µM) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 ± 0.1 µM) while the 9-deazahypoxanthine derivative of l-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 ± 1.3 µM) and prominent effect on L1210/0 (IC50 = 4.5 ± 0.5 µM). Furthermore, the 9-deazapurine derivative disubstituted with two imino-l-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 ± 0.3 µM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 ± 0.2 µM). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of l-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells.


Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Citomegalovirus/efeitos dos fármacos , Purinas/química , Purinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antivirais/síntese química , Antivirais/química , Ácido Ascórbico/síntese química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Purinas/síntese química , Relação Estrutura-Atividade
7.
Bioorg Med Chem ; 20(11): 3675-85, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22555152

RESUMO

Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 ± 4 and 7.3 ± 0.1 µM, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Ácido Ascórbico/análogos & derivados , Hepacivirus/efeitos dos fármacos , Imidazóis/química , Triazóis/química , Animais , Antineoplásicos/química , Antivirais/química , Ácido Ascórbico/química , Linhagem Celular Tumoral , Cães , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Hepacivirus/fisiologia , Humanos , IMP Desidrogenase/antagonistas & inibidores , Imidazóis/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Replicação Viral/efeitos dos fármacos
8.
Drug Resist Updat ; 9(3): 142-56, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16899402

RESUMO

In gram-negative bacteria, beta-lactamases are the most important mechanism of resistance to beta-lactam antibiotics. Currently, the beta-lactamases receiving the most attention are the extended-spectrum beta-lactamases (ESBLs), inhibitor-resistant beta-lactamases and carbapenemases. When found in Escherichia coli and Klebsiella spp., ESBLs confer resistance to extended-spectrum cephalosporins, such as ceftazidime, cefotaxime and cefepime. Hence, ESBLs limit the choice of beta-lactam therapy to carbapenems. A worrisome trend is the increasing number of pathogens found in isolates from patients in the community that possess ESBLs. It is equally distressing that carbapenemases (serine and metallo-beta-lactamases) are being found in many of the same bacteria that harbor ESBLs, for example Klebsiella pneumoniae. Despite many years studying beta-lactamases, important clinical and scientific questions still remain.


Assuntos
Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Farmacorresistência Bacteriana/fisiologia , beta-Lactamases/fisiologia , Animais , Bactérias/genética , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Inibidores de beta-Lactamases , beta-Lactamases/classificação , beta-Lactamases/genética , beta-Lactamases/metabolismo , beta-Lactamas/farmacologia
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