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1.
J Hosp Infect ; 146: 224-231, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37094715

RESUMO

BACKGROUND: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency. METHODS: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method. RESULTS: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method. CONCLUSION: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV.

2.
Eur Rev Med Pharmacol Sci ; 27(6): 2561-2570, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013774

RESUMO

OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms. MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression. RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression. CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias do Colo , Neoplasias Pulmonares , Metiltransferases , Fatores de Processamento de Serina-Arginina , Humanos , Carcinogênese , Regulação para Baixo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metiltransferases/genética , Fatores de Processamento de Serina-Arginina/genética
3.
Int J Tuberc Lung Dis ; 25(12): 974-981, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34886926

RESUMO

BACKGROUND: The mechanism underlying kanamycin (KM) resistance in Mycobacterium tuberculosis is not well understood, although efflux pump proteins are thought to play a role. This study used RNA-seq data to investigate changes in the expression levels of efflux pump genes following exposure to KM.METHODS: RNA expression of efflux pump and regulatory genes following exposure to different concentrations of KM (minimum inhibitory concentration MIC 25 and MIC50) in rrs wild-type strain and rrs A1401G mutated strain were compared with the control group.RESULTS: The selected strains had differential RNA expression patterns. Among the 71 putative efflux pump and regulatory genes, 46 had significant fold changes, and 12 genes (Rv0842, Rv1146, Rv1258c, Rv1473, Rv1686c, Rv1687c, Rv1877, Rv2038c, Rv3065, Rv3197a, Rv3728 and Rv3789) that were overexpressed following exposure to KM were thought to contribute to drug resistance. Rv3197A (whiB7) showed a distinct fold change based on the concentration of KM.CONCLUSION: The significant changes in the expression of the efflux pump and regulatory genes following exposure to KM may provide insights into the identification of a new resistance mechanism.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , RNA-Seq , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
4.
Eur Rev Med Pharmacol Sci ; 24(12): 6893-6898, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633382

RESUMO

OBJECTIVE: Primary headache disorders in children are one of the most prominent topics in the pediatric neurology literature. However, there are many unsolved aspects, including the conditions associated with migraine. The present study aims to report on the frequency of behavioral comorbidities in the setting of primary headache in childhood. PATIENTS AND METHODS: In this study, we enlisted 475 children (290 males and 185 females; ratio 1.6:1), aged 4 to 14 years, who were affected by primary headache. In direct interviews, children and parents gave information on the association of their headache with, attention-deficit/hyperactivity disorder, learning disabilities, tics, anxiety, depression, and obsessive-compulsive disorder. Other 475 children with no history of headache or recognized neurological conditions were matched for age, sex, race, and socioeconomic status and were used as controls. RESULTS: A significant association of primary headache was found with anxiety and depression (p-value <0.001); overall, behavioral disorders were more common in children who experienced headache than in controls (p-value <0.001). CONCLUSIONS: Primary headache in children is not associated with most of the common behavioral conditions. On the contrary, there was a significant association with anxiety and depression, as reported in adults.


Assuntos
Transtornos de Ansiedade/complicações , Depressão/complicações , Cefaleia/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Itália , Masculino , Classe Social
5.
Br J Dermatol ; 181(6): 1216-1225, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30801661

RESUMO

BACKGROUND: Oxytocin (OT) is a neuropeptide hormone that has many beneficial biological effects, including protection against age-related disorders. However, less is known about its role in intrinsic skin ageing, which is accelerated by an increase in senescent cell fraction in skin tissue. OBJECTIVES: To investigate the novel function and the underlying mechanism of OT in preventing cellular senescence in normal human dermal fibroblasts (NHDFs) isolated from the skin of female donors of different ages. METHODS: NHDFs from young and old donors were exposed to conditioned medium from senescent or control NHDFs in the presence or absence of 10 nmol L-1 OT for 3 days, and were continuously subcultured for 12 days. Subsequently, various age-associated signs of senescence including decreased proliferation rate, elevated p16 and p21 levels, and positivity for senescence-associated ß-galactosidase expression were examined. RESULTS: We found that OT suppressed senescence-associated secretory phenotype-induced senescence in NHDFs, and its effect depended on the age of the donor's NHDFs. The inhibitory effects of OT required signalling by OT receptor-mediated extracellular signal-regulated kinase/Nrf2 (nuclear factor erythroid 2-related factor 2). The age-dependent antisenescence effects of OT are closely related to hypermethylation of the OT receptor gene (OXTR). CONCLUSIONS: Our findings bring to light the role of OT in the prevention of skin ageing, which might allow development of new clinical strategies. What's already known about this topic? Senescent keratinocytes and fibroblasts accumulate with age in the skin and contribute to the loss of skin function and integrity during ageing. Senescent cells secrete senescence-associated secretory phenotype (SASP), which includes the release of proinflammatory cytokines such as interleukin (IL)-6 and IL-1, chemokines, extracellular matrix-remodelling proteases and growth factors. The neuropeptide oxytocin (OT) and its receptor (OXTR) have protective effects against various age-related disorders. What does this study add? OT suppressed SASP-induced cellular senescence in normal human dermal fibroblasts (NHDFs), depending on the age of the NHDFs' donor. The inhibitory effects of OT on cellular senescence required OXTR-mediated phosphorylation of extracellular signal-regulated kinase, which enhanced nuclear localization of Nrf2, a vital factor in the antioxidant defence system. The age-specific antisenescent effects of OT were closely related to hypermethylation of OXTR. What is the translational message? Our results suggest that OT and OXTR agonists could be clinically promising agents for the improvement of age-associated skin ageing, especially in women.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Envelhecimento da Pele/fisiologia , Adulto , Fatores Etários , Idoso , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Metilação de DNA , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Feminino , Fibroblastos/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pessoa de Meia-Idade , Ocitocina/farmacologia , Receptores de Ocitocina/agonistas , Receptores de Ocitocina/genética , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Adulto Jovem
6.
Clin Microbiol Infect ; 25(5): 546-554, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30448331

RESUMO

BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.


Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Stenotrophomonas maltophilia/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stenotrophomonas maltophilia/isolamento & purificação , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
7.
Int J Obes (Lond) ; 42(4): 755-764, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29762555

RESUMO

OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses. RESULTS: In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns. CONCLUSIONS: Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.


Assuntos
Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Transcriptoma/fisiologia , Aumento de Peso/imunologia , Aumento de Peso/fisiologia , Tecido Adiposo Branco/química , Animais , Perfilação da Expressão Gênica , Gônadas/química , Gônadas/metabolismo , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
J Endocrinol Invest ; 41(4): 475-483, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29103133

RESUMO

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.


Assuntos
Estatura/efeitos dos fármacos , Nanismo/tratamento farmacológico , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Puberdade , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , República da Coreia
9.
Eur J Clin Microbiol Infect Dis ; 36(11): 2179-2186, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28695355

RESUMO

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes Sorológicos/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Sensibilidade e Especificidade
10.
Eur J Clin Microbiol Infect Dis ; 36(7): 1091-1096, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28078559

RESUMO

To evaluate effect of empirical combination of a ß-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, ß-lactam; VAN group, vancomycin; BV group, combination of ß-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086-3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a ß-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , beta-Lactamas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/mortalidade , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
11.
Int J Impot Res ; 29(1): 23-29, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27654033

RESUMO

Diabetes-induced ED correlates with diabetes duration and glycemic control. This study evaluated the effect of glycemic control start time on erectile function in streptozotocin-induced diabetic rats. Rats were divided into normal controls (C); untreated diabetic rats (DM); and rats treated after 7 weeks (7W), and 10 weeks (10W) from DM. Treated diabetic rats received a timed daily injection of insulin. After 14 weeks of lab-controlled diabetes, experiments were performed. Group DM showed the ratio of intracavernosal pressure, significantly lower than other groups (10W vs DM; P<0.001). Groups 7W and 10W responded similarly, but did not recover to normal level (group C vs 7W; P<0.001). The percentage of α-smooth muscle actin increased more with earlier start times, and group DM's percentages decreased significantly (group 10W vs DM; P<0.001). Apoptosis recovered significantly only in group 7W, comparable to group C. As start times became earlier, for all molecules (eNOS, Akt, MYPT1 and PECAM-1), treatment groups' results neared those of group C. In conclusion, erectile function of diabetic rats recovered closer to normal controls if diabetic treatment started earlier. And the level of glycemic control was expected to be more important than the start time of diabetic treatment.


Assuntos
Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/administração & dosagem , Ereção Peniana/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Índice Glicêmico , Masculino , Óxido Nítrico Sintase Tipo III , Ratos , Ratos Sprague-Dawley , Estreptozocina , Fatores de Tempo
12.
Prostate Cancer Prostatic Dis ; 19(3): 223-30, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27136743

RESUMO

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a cell surface enzyme that is highly expressed in prostate cancer (PCa) and is currently being extensively explored as a promising target for molecular imaging in a variety of clinical contexts. Novel antibody and small-molecule PSMA radiotracers labeled with a variety of radionuclides for positron emission tomography (PET) imaging applications have been developed and explored in recent studies. METHODS: A great deal of progress has been made in defining the clinical utility of this class of PET agents through predominantly small and retrospective clinical studies. The most compelling data to date has been in the setting of biochemically recurrent PCa, where PSMA-targeted radiotracers have been found to be superior to conventional imaging and other molecular imaging agents for the detection of locally recurrent and metastatic PCa. RESULTS: Early data, however, suggest that initial lymph node staging before definitive therapy in high-risk primary PCa patients may be limited, although intraoperative guidance may still hold promise. Other examples of potential promising applications for PSMA PET imaging include non-invasive characterization of primary PCa, staging and treatment planning for PSMA-targeted radiotherapeutics, and guidance of focal therapy for oligometastatic disease. CONCLUSIONS: However, all of these indications and applications for PCa PSMA PET imaging are still lacking and require large, prospective, systematic clinical trials for validation. Such validation trials are needed and hopefully will be forthcoming as the fields of molecular imaging, urology, radiation oncology and medical oncology continue to define and refine the utility of PSMA-targeted PET imaging to improve the management of PCa patients.


Assuntos
Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Imagem Molecular , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Terapia Combinada , Humanos , Masculino , Imagem Molecular/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/terapia , Traçadores Radioativos , Compostos Radiofarmacêuticos/química , Recidiva , Resultado do Tratamento
14.
Hong Kong Med J ; 21(4): 339-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26183452

RESUMO

OBJECTIVES: To identify the major causes and types of dental luxation and avulsion injuries, and their associated factors in primary school children in Hong Kong. DESIGN: Case series. SETTING: School dental clinic, New Territories, Hong Kong. PATIENTS: The dental records of children with a history of dental luxation and/or avulsion injury between November 2005 and October 2012 were reviewed. Objective clinical and radiographical findings at the time of injury and at follow-up examinations were recorded using a standardised form. Data analysis was carried out using the Chi squared test and multinomial logistic regression. RESULTS: A total of 220 children with 355 teeth of dental luxation or avulsion injury were recorded. Their age ranged from 6 to 14 years and the female-to-male ratio was 1:1.8. The peak occurrence was at the age of 9 years. Subluxation was the most common type of injury, followed by concussion. Maxillary central incisors were the most commonly affected teeth. The predominant cause was fall and most injuries occurred at school. Incisor relationship was registered in 199 cases: most of them were Class I. Comparison of the incisor relationship in study children and the general Chinese population in another study revealed a higher proportion of Class II and fewer Class III occlusions in the trauma group (P<0.0001). CONCLUSION: Most dental luxation and avulsion injuries in Hong Kong primary school children are caused by fall. Boys are more commonly affected than girls, and a Class II incisor relationship is a significant risk factor.


Assuntos
Incisivo/lesões , Instituições Acadêmicas/estatística & dados numéricos , Avulsão Dentária/etiologia , Acidentes por Quedas/estatística & dados numéricos , Adolescente , Povo Asiático/estatística & dados numéricos , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Distribuição de Qui-Quadrado , Criança , Oclusão Dentária , Feminino , Hong Kong/epidemiologia , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Avulsão Dentária/epidemiologia
15.
Q J Nucl Med Mol Imaging ; 59(3): 241-68, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26213140

RESUMO

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers.


Assuntos
Antígenos de Superfície/química , Glutamato Carboxipeptidase II/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Animais , Cristalografia por Raios X , Desenho de Fármacos , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Modelos Moleculares , Imagem Molecular/métodos , Nanomedicina/métodos , Nanomedicina/tendências , Nanopartículas/química , Metástase Neoplásica , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Nanomedicina Teranóstica , Ureia/química
16.
Eur J Clin Microbiol Infect Dis ; 34(7): 1437-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25894983

RESUMO

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.


Assuntos
Antibacterianos/efeitos adversos , Mananas/sangue , Neoplasias/sangue , Ácido Penicilânico/análogos & derivados , Piperacilina/efeitos adversos , Adulto , Idoso , Antibacterianos/administração & dosagem , Antígenos de Fungos/sangue , Aspergilose/sangue , Aspergilose/etiologia , Estudos de Casos e Controles , Reações Falso-Positivas , Feminino , Galactose/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Estudos Retrospectivos , Tazobactam , Fatores de Tempo
17.
Transpl Infect Dis ; 17(1): 73-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25620389

RESUMO

BACKGROUND: Few reports discuss the optimal management of patients diagnosed with tuberculosis (TB) before scheduled stem cell transplantation (SCT), who then proceed with transplantation. METHODS: We found 13 patients with TB before SCT (proven, n = 9; probable, n = 3; possible, n = 1) in the medical records of our institution. RESULTS: Most of the patients had pulmonary TB (n = 8; disseminated, n = 2; extrapulmonary, n = 3). Eight of 9 patients with proven disease had SCT after at least 100 days of anti-tuberculous medication, ranging from 103 to 450 days. None of those patients suffered TB-related events after SCT. However, 1 patient with proven pulmonary TB who underwent SCT after only 40 days of anti-tuberculous therapy subsequently died of TB meningitis. Patients with possible and probable disease had their transplants after 6-176 days of anti-tuberculous medication, and all were alive at the time of analysis. The entire duration of anti-tuberculous medication was 12 months in most cases. With a follow-up duration ranging from 0.7 to 87.5 months, 4 patients died, but TB was the cause of death in only 1 case. CONCLUSION: In conclusion, for proven cases of TB, SCT after >100 days of anti-tuberculous medication is probably feasible and safe, in terms of TB control, in patients with various hematologic diseases.


Assuntos
Antituberculosos/uso terapêutico , Doenças Hematológicas/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Tuberculose Pulmonar/complicações
18.
Neurogastroenterol Motil ; 27(2): 212-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25376877

RESUMO

BACKGROUND: Dysphagia is considered an alarm symptom but detailed population-based data on dysphagia are lacking. We aimed to estimate in a representative USA Caucasian population, the prevalence of dysphagia and potential risk factors. METHODS: A modified version of the previously validated Bowel Disease Questionnaire was mailed to a population-based cohort (n = 7640) of Olmsted County, MN. Dysphagia was measured by one validated question 'In the last year, how often have you had difficulty swallowing (a feeling that food sticks in your throat or chest)?' The medical records were reviewed for organic causes of dysphagia. The associations of reported frequency of dysphagia with potential risk factors were assessed using logistic regression models. KEY RESULTS: The sex-specific, age-adjusted (US White 2000) prevalence for dysphagia experienced at least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0) in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3, 1.8). Gastro-esophageal reflux disease (GERD) was the most common diagnosis in those reporting dysphagia on the medical record; other organic explanations were rare and only found in the frequent dysphagia group. CONCLUSIONS & INFERENCES: Frequent dysphagia is not rare in the community (3%), occurs in both women and men across all adult age groups, and is most likely to indicate underlying GERD.


Assuntos
Transtornos de Deglutição/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Prevalência , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia , População Branca
19.
Clin Lab ; 60(8): 1413-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25185431

RESUMO

BACKGROUND: Smoking is considered as a major modifiable risk factor for cardiovascular diseases. It has been shown that smoking cessation drops the risk of cardiovascular diseases such as myocardial infarction and also improves platelet function. Because mean platelet volume (MPV) is a simple and convenient indicator for platelet activation, we planned to investigate the effect of smoking status on MPV in healthy populations. METHODS: This study was conducted on 398 individuals who visited our hospital for regular medical check-ups and were confirmed not to have diabetes or hypertension. MPV was measured using EDTA blood on an Advia 2120 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) within 2 hours. RESULTS: Present smokers showed higher MPV levels than present non-smokers. When MPV was compared by taking previous smoking history and present smoking status into account, the smoking cessation group showed significantly lower MPV levels than other groups. CONCLUSIONS: Because this finding was significant only in the female group, the change in MPV according to smoking status was found to be different by gender. We carefully suggest that smoking cessation can lower the risk of cardiovascular diseases through the change in MPV, which can be more effective for women than men.


Assuntos
Plaquetas/citologia , Volume Plaquetário Médio , Abandono do Hábito de Fumar , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Ácido Edético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores Sexuais , Adulto Jovem
20.
Eur J Clin Microbiol Infect Dis ; 33(10): 1847-53, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24853055

RESUMO

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Gastroenterite/epidemiologia , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reação Transfusional
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