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Schwannomatosis is characterized by the presence of multiple schwannomas without landmarks of NF2. It is considered the rarest form of neurofibromatosis (NF). Here, we report the first case of familial schwannomatosis with regard to the segmental/generalized phenotype, in which the proband and the daughter present a distinct phenotype in this classification. The proband presents a generalized, painless, extradural type of schwannomatosis, while the daughter shows a segmental, painful, intradural type of schwannomatosis. Whole-exome sequencing of the affected individuals revealed a shared novel SMARCB1 gene mutation (c.92A > G, p.Glu31Gly) despite the clinical variability. We thus suggest two points in the diagnosis of familial schwannomatosis: The identified novel germline SMARCB1 variant can be reflective of a phenotypical progression from a segmental to a generalized type of schwannomatosis, or an intrafamilial variability in inherited schwannomatosis, which was not reported in previous literature. The specific combination of somatic NF2 mutations may be a major factor in regulating the severity and scope of the resulting phenotype in schwannomatosis.
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Neurilemoma , Neurofibromatoses , Neoplasias Cutâneas , Humanos , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Proteínas Cromossômicas não Histona/genética , Neurofibromatoses/genética , Neurilemoma/genética , Neurilemoma/diagnóstico , Neoplasias Cutâneas/genética , Mutação em Linhagem Germinativa/genética , Proteína SMARCB1/genéticaRESUMO
This observational study aimed to evaluate the prognostic significance of interim and final 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) responses to upfront autologous stem cell transplantation (ASCT) in patients with peripheral T cell lymphomas (PTCLs). A total of 118 patients, from two independent institutions, with newly diagnosed PTCLs were enrolled, and 96 of them were evaluated. PET/CT was assessed at diagnosis, and during and after the primary treatment. Clinical outcomes of interim and final PET/CT were compared between transplanted and non-transplanted patients. The responses of PET/CT were assessed based on visual analysis using the Deauville five-point scale (5-PS). Clinicopathological features of transplanted patients (n = 37) were similar to those of non-transplanted patients (n = 59). After a median follow-up of 60.8 months, only final PET/CT response based on 5-PS was the independent prognostic factor of survival outcome (P < 0.001; HR 8.215; 95% C.I. 2.97-22.72) in multivariate analysis. Interim PET/CT response did not have a differential potential for predicting progression-free survival (PFS). In 59 patients, with score 1 or 2 in final PET/CT, the PFS rate was not significantly different between transplanted and non-transplanted patients (P = 0.970). Moreover, among the 37 patients with final PET/CT response score of 3-4, the PFS rate was equally poor in both transplanted and non-transplanted patients (P = 0.178). Final PET/CT assessment, based on 5-PS, was an important prognostic parameter for primary treatment of PTCLs, regardless of upfront ASCT. Interim PET/CT response could not be an indicator to determine the requirement for upfront ASCT.
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Fluordesoxiglucose F18/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Adulto , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is essential for the uptake of radioiodine into thyroid remnants and residual thyroid cancer in patients undergoing high-dose radioiodine therapy (HD-RIT). Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased in preference over the conventional method of thyroid hormone withdrawal (THW). However, the clinical influences of the two methods, aside from the therapeutic effects, have not been widely evaluated. The aim of this work was to investigate the influences of the two methods, particularly on the renal function and external radiation dose rate (EDR) from patients undergoing HD-RIT. METHODS: From February 2012 to November 2016, 667 patients (M:F=138:529, mean age: 47.7±11.8 years), who underwent first HD-RIT (120, 150, or 180 mCi, 1 mCi=37 MBq) for ablation of remnant thyroid tissue or residual thyroid cancer, were enrolled. Patients who were proven to have distant metastasis to lung or bone were excluded. Low- to high-risk patients based on 2015 American thyroid association management guidelines who underwent first HD-RIT in our department were included. The period from total thyroidectomy to HD-RIT was limited within 12 months. The following parameters were collected and evaluated: age, gender, histology type and TNM stage of thyroid cancer, glomerular filtration rate on the admission day for total thyroidectomy (baseline GFR), GFR on the day of HD-RIT (follow-up GFR), thyroglobulin (Tg) and TSH levels on the day of HD-RIT, and EDR on the discharge day after HD-RIT. RESULTS: There were 386 patients using the THW method and 281 patients choosing the rh-TSH method. The baseline GFR of the THW group (106±16 mL/min/1.73 m2) and that of the rh-TSH group (104±17 mL/min/1.73 m2) were within normal limits and there was no significant difference. However, follow-up GFR of the THW group (84±17 mL/min/1.73 m2) was much lower than that of the rh-TSH group (104±16 mL/min/1.73 m2) (P=0.000). In the THW group, the follow-up GFR decreased significantly (P=0.000), yet the follow-up GFR of the rh-TSH group was not statistically different when compared with its baseline GFR (P=0.142). EDRs were lower in all rh-TSH subgroups compared to those of THW subgroups with statistical significance. Tg and TSH levels were not different between the two groups, excluding a few small-sized subgroups analyses. CONCLUSIONS: In this retrospective analysis of renal function and EDR, the use of rh-TSH appears to help maintain renal function and finally decrease EDR in contrast to the THW method when undergoing HD-RIT.
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Técnicas de Ablação , Radioisótopos do Iodo/uso terapêutico , Rim/fisiopatologia , Alta do Paciente , Doses de Radiação , Neoplasias da Glândula Tireoide/fisiopatologia , Neoplasias da Glândula Tireoide/radioterapia , Feminino , Humanos , Rim/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.
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Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: The utility of [18F]FDG PET/CT for characterizing malignant ovarian mass has not been extensively studied. Here, we investigated various parameters that could be useful to differentiate malignant ovarian mass. METHODS: We enrolled 51 female patients (53.4±15.0 years), with 86 ovarian masses, who underwent pretreatment [18F]FDG PET/CT. Thirty six lesions were histopathologically confirmed with ovarian serous adenocarcinoma. Thirty one ovarian masses from gastric cancer and 19 masses from colorectal cancer were diagnosed by histopathological study or clinical follow-up. Ovarian masses were evaluated by size, solidity, and metabolic indices. The degree of solidity was scored from 1 to 5 according to the portion of solid and cyst. Metabolic activity was scored to be either positive (≥ liver) or negative (< liver). SUVmax (SUVovary) and the ratio of SUVmax of ovary to SUVmean of the liver (ovary/L ratio) were performed. Age, bilaterality and level of CA 125 were also compared. In statistical analysis, categorical variables were analyzed using Pearson's chi-square test, while continuous variables were evaluated either independent student's t-test or Mann-Whitney Test. Receiveroperating-characteristic analysis was used to obtain optimal cutoff values. RESULTS: Serous adenocarcinoma had significantly higher score in all metabolic indices over metastasis. However, there were no differences in all metabolic indices in ovarian metastasis. In contrast, solidity was different between metastatic mass from gastric and colorectal cancer. Ovarian metastasis from gastric cancer was significantly solid compared with that from colorectal cancer. In comparison of all three masses, solidity and all metabolic indices were significantly different. Patients with serous adenocarcinoma were older and had higher CA-125 level. Between metastases from gastric and colorectal cancer, there were no differences in age, bilaterality and CA-125. CONCLUSIONS: Metabolic indices such as SUVovary and ovary/L ratio could be useful to differentiate serous adenocarcinoma from metastasis. Furthermore, the degree of solidity could play a role in predicting the origin of metastasis.
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Fluordesoxiglucose F18 , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Carga TumoralRESUMO
PURPOSE: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs. METHODS: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients. RESULTS: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort. CONCLUSION: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.
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Linfoma de Células T Periférico/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células T Periférico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Medição de RiscoRESUMO
Unfortunately, the original version of this article contained several errors made during final step of article production. In the results section (fourth sentence) of the Abstract, the incomplete sentence,", 31.4% in high-risk group and 4.7% in treatment failure group.
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BACKGROUND: The aim of this study was to find a reliable predictor of recurrence in patients with locally advanced colorectal cancer. METHODS: We enrolled 96 patients for this retrospective study. We investigated metabolic (SUVmax, metabolic tumor volume, total lesion glycolysis, and heterogeneity), clinical (age, sex, stage, and CEA level) and pathologic (Ki-67, p53, CD31, COX-2, E-cadherin and EGFR) parameters. The coefficient of variation (COV) was chosen to assess heterogeneity of [18F]FDG uptake by dividing the standard deviation of the SUV by SUVmean. Recurrence-free survival was compared with each metabolic, clinical and pathologic parameters by using univariate and multivariate survival analysis. RESULTS: Among 96 patients, 19 patients (19.8%) showed disease recurrence. In the ROC analysis, the optimal cutoff values of SUVmax, metabolic tumor volume (cm3), total lesion glycolysis (cm3), and metabolic heterogeneity were determined as 17.6, 10.05, 232.46, and 0.48, respectively. In univariate analysis, probability of recurrence was statistically increased in those with metabolic tumor volume >10.05 (P=0.045), and those with metabolic heterogeneity >0.48 (P=0.031). In multivariate analysis, metabolic heterogeneity was the only independent prognostic factor (HR 4.56, 95% CI 1.57-13.23, P=0.006). CONCLUSIONS: Intratumoral metabolic heterogeneity assessed by COV is a reliable predictive factor for disease recurrence in patients with locally advanced colorectal cancer. Therefore, its application could be an important step for personalized management of colorectal cancer.
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Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/metabolismo , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos RetrospectivosRESUMO
INTRODUCTION: Mild hyperthermia has been known to enhance the response of tumours to radiotherapy or chemotherapy by increasing tumour blood flow, thereby increasing tumour oxygenation or drug delivery. The purpose of this study was to assess the changes in temperature and blood flow in human cervical cancer in response to regional heating with modulated electro-hyperthermia (mEHT). METHODS: The pelvic area of 20 patients with cervical carcinoma was heated with mEHT. The peri-tumour temperature was measured using an internal organ temperature probe. The tumour blood flow was measured using 3D colour Doppler ultrasound by determining the peak systolic velocity/end-diastolic velocity ratio (S/D ratio) and the resistance index (RI) within blood vessels. RESULTS: The mean peri-tumour temperature was 36.7 ± 0.2 °C before heating and increased to 38.5 ± 0.8 °C at the end of heating for 60 min. The marked declines in RI and S/D values strongly demonstrated that heating significantly increased tumour blood perfusion. CONCLUSIONS: Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.
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Hipertermia Induzida/métodos , Fluxo Sanguíneo Regional/fisiologia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Temperatura , Neoplasias do Colo do Útero/patologiaRESUMO
An 11-year-old boy underwent a bone single-photon emission computed tomography/computed tomography (SPECT/CT) scan 3 months after fracturing his right tibia. The standardized uptake values (SUVs) of the growth plates in his right tibia were higher compared to those in the left tibia. One year later, the right leg was 10 mm longer than the left leg with higher SUVs in the right tibial growth plates. After performing epiphysiodesis at the right proximal tibia, the leg-length difference (LLD) decreased from 17 to 12 mm with the decrease of SUVs in the growth plates of the right tibia. This case emphasizes the potential of quantitative analysis using bone SPECT/CT in predicting LLD and determining the necessity of length equalization surgery in pediatric lower limb fractures.
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ABSTRACT: A 51-year-old woman who had a history of partial nephrectomy underwent an 18 F-FDG PET/CT image for a routine health checkup. Focal intense FDG avidity without any anatomical correlation on CT was detected in the lung. On the delayed image after 20 minutes, the focal activity migrated to a more peripheral portion. An iatrogenic microembolus is a rare but crucial false-positive finding that nuclear physicians should be aware of. Our case emphasizes the importance of meticulous FDG injection and cautious interpretation. In addition, delayed PET/CT imaging through wet reading can aid in diagnosing and help prevent unnecessary investigations.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons , Doença IatrogênicaRESUMO
BACKGROUND: Bone scintigraphy is emerging as a confirmatory diagnostic tool for transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to investigate the frequency and clinical characteristics of patients with incidental cardiac uptake and incidental ATTR-CA on bone scintigraphy. METHODS: All bone scintigraphic studies performed at a tertiary teaching hospital between 2011 and 2022 were reviewed retrospectively. Patients who underwent bone scintigraphy to confirm ATTR-CA were excluded. Patients with cardiac uptake of grade 2 or 3 were included and divided into two groups: possible ATTR-CA group and noncardiac amyloidosis (non-CA) group. RESULTS: Of the 61,432 bone scintigraphic studies performed on 32,245 patients, 23 (0.07%) had grade 2 or 3 cardiac uptake. Nine of 23 patients (39.1%) were assigned to the non-CA group because they showed cardiac uptake from definite other causes or focal uptake that did not match CA. The remaining 14 patients (60.9%) were classified as the possible ATTR-CA group, and five patients were referred to cardiologists and finally diagnosed with ATTR-CA. Two patients were treated with tafamidis. Patients in the ATTR-CA group were significantly older and had a less frequent history of end-stage renal disease than those in the non-CA group. Other characteristics were comparable in both groups. CONCLUSIONS: Although incidental ATTR-CA in patients undergoing bone scintigraphy for noncardiac reasons is uncommon, if cardiac uptake is observed in elderly patients without metastatic calcification associated with end-stage renal disease, further diagnostic work-up for ATTR-CA as a cause of undiagnosed heart failure should be considered.
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RATIONALE: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial. PATIENT CONCERNS: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan. DIAGNOSES: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake. INTERVENTIONS: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy. OUTCOMES: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months. LESSONS: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.
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Adenocarcinoma Folicular , Achados Incidentais , Neoplasias das Paratireoides , Tecnécio Tc 99m Sestamibi , Humanos , Feminino , Adulto , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/diagnóstico , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/cirurgia , Diagnóstico Diferencial , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico , Compostos Radiofarmacêuticos , Adenoma/diagnóstico por imagem , Adenoma/diagnóstico , Adenoma/cirurgia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.
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Fluordesoxiglucose F18 , Lúpus Eritematoso Sistêmico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tifo por Ácaros , Humanos , Tifo por Ácaros/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Baço/diagnóstico por imagem , Baço/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/metabolismo , Diagnóstico Diferencial , Compostos Radiofarmacêuticos , Adulto JovemRESUMO
This experimental study aimed to evaluate the antiviral and synergistic effects of photoenergy irradiation on human herpes simplex virus type I (HSV-1) infection. We assessed viral replication, plaque formation, and relevant viral gene expression to examine the antiviral and synergistic effects of blue light (BL) with acyclovir treatment. Our results showed that daily BL (10 J/cm2) irradiation inhibited plaque-forming ability and decreased viral copy numbers in HSV-1-infected monkey kidney epithelial Vero cells and primary human oral keratinocyte (HOK) cells. Combined treatment with the antiviral agent acyclovir and BL irradiation increased anti-viral activity, reducing viral titers and copy numbers. In particular, accumulated BL irradiation suppressed characteristic viral genes including UL19 and US6, and viral DNA replication-essential genes including UL9, UL30, UL42, and UL52 in HOK cells. Our results suggest that BL irradiation has anti-viral and synergistic properties, making it a promising therapeutic candidate for suppressing viral infections in clinical trials.
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Aciclovir , Antivirais , Herpesvirus Humano 1 , Replicação Viral , Antivirais/farmacologia , Animais , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos da radiação , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 1/genética , Chlorocebus aethiops , Células Vero , Humanos , Replicação Viral/efeitos dos fármacos , Replicação Viral/efeitos da radiação , Aciclovir/farmacologia , Luz , Herpes Simples/virologia , Herpes Simples/tratamento farmacológico , Queratinócitos/virologia , Queratinócitos/efeitos da radiação , Queratinócitos/efeitos dos fármacos , Ensaio de Placa ViralRESUMO
Despite current immunosuppressive therapies, acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, therapeutic effects of intraperitoneal glutamine (Gln) administration (1g/kg/day) in a mouse aGVHD model were evaluated. Gln administration significantly inhibited the GVHD-induced inflammation and tissue injury in the intestine, liver, skin and spleen. Gln therapy improved the score of clinical evidence of aGVHD and prolonged the median survival of aGVHD mice. Gln administration in aGVHD mice increased the fraction of Foxp3+/CD4+/CD25+ cells in the blood measured on day 7, and decreased the serum levels of tumor necrosis factor-α measured on days 7, 14 and 21 after aGVHD induction. These results demonstrated that Gln administration may be useful in protecting the host from aGVHD.
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Transplante de Células/métodos , Glutamina/farmacologia , Doença Enxerto-Hospedeiro/prevenção & controle , Baço/citologia , Doença Aguda , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Transplante de Células/efeitos adversos , Feminino , Fatores de Transcrição Forkhead/sangue , Glutamina/administração & dosagem , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Inflamação/prevenção & controle , Injeções Intraperitoneais , Interferon gama/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Intestinos/efeitos dos fármacos , Intestinos/patologia , Contagem de Leucócitos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Pele/patologia , Análise de Sobrevida , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
In contrast to the well known immunostimulatory roles of IL-12, little has been known about its immunosuppressive roles. In the present study, IL-12-activated lymphocyte-mediated macrophage apoptosis was investigated by employing murine lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by blocking antibodies to IFN-γ and TNF-α, suggesting the key role of these lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO inhibited macrophage proliferation, and induced apoptosis in concordance with the accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger). These results were further supported by the findings obtained from the experiments employing IFN-γ-knockout and iNOS-knockout mice. Our study demonstrated a novel, non-contact-dependent mechanism of macrophage suppression by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages due to endogenous NO synthesis induced by cytokines secreted from IL-12-activated lymphocytes.
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Apoptose/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-12/farmacologia , Macrófagos/imunologia , Animais , Anticorpos Bloqueadores/imunologia , Apoptose/imunologia , Benzoatos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Caspase 3/metabolismo , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Guanidinas/metabolismo , Imidazóis/metabolismo , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , ômega-N-Metilarginina/metabolismoRESUMO
BACKGROUND: The objective of the study was to compare the diagnostic efficacy of an integrated Fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT-mammography (mammo-PET/CT) with conventional torso PET/CT (supine-PET/CT) and MR-mammography for initial assessment of breast cancer patients. PATIENTS AND METHODS: Forty women (52.0 ± 12.0 years) with breast cancer who underwent supine-PET/CT, mammo-PET/CT, and MR-mammography from April 2009 to August 2009 were enrolled in the study. We compared the size of the tumour, tumour to chest wall distance, tumour to skin distance, volume of axillary fossa, and number of meta-static axillary lymph nodes between supine-PET/CT and mammo-PET/CT. Next, we assessed the difference of focality of primary breast tumour and tumour size in mammo-PET/CT and MR-mammography. Histopathologic findings served as the standard of reference. RESULTS: In the comparison between supine-PET/CT and mammo-PET/CT, significant differences were found in the tumour size (supine-PET/CT: 1.3 ± 0.6 cm, mammo-PET/CT: 1.5 ± 0.6 cm, p < 0.001), tumour to thoracic wall distance (1.8 ± 0.9 cm, 2.2 ± 2.1 cm, p < 0.001), and tumour to skin distance (1.5 ± 0.8 cm, 2.1 ± 1.4 cm, p < 0.001). The volume of axillary fossa was significantly wider in mammo-PET/CT than supine-PET/CT (21.7 ± 8.7 cm(3) vs. 23.4 ± 10.4 cm(3), p = 0.03). Mammo-PET/CT provided more correct definition of the T-stage of the primary tumour than did supine-PET/CT (72.5% vs. 67.5%). No significant difference was found in the number of metastatic axillary lymph nodes. Compared with MR-mammography, mammo-PET/CT provided more correct classification of the focality of lesion than did MR-mammography (95% vs. 90%). In the T-stage, 72.5% of cases with mammo-PET/CT and 70% of cases with MR-mammography showed correspondence with pathologic results. CONCLUSIONS: Mammo-PET/CT provided more correct definition of the T-stage and evaluation of axillary fossa may also be delineated more clearly than with supine-PET/CT. The initial assessment of mammo-PET/CT would be more useful than MR-mammography because the mammo-PET/CT indicates similar accuracy with MR-mammography for decision of T-stage of primary breast tumour and more correct than MR-mammography for defining focality of lesion.
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ABSTRACT: A 58-year-old man with fever, myalgia, and dysuria was admitted to the hospital. Because of prolonged fever, FDG PET/CT was performed. Surprisingly, bilateral kidneys were rapidly enlarged for 5 days with the renal parenchyma showing intense hypermetabolism. FDG PET/CT demonstrated physiology of Hantavirus invading kidneys and causing nephritis. This case illustrates that FDG PET/CT could be the choice of image modality for diagnosis and treatment evaluation of patients suspected of hemorrhagic fever with renal syndrome. To the best of our knowledge, this is the first report of FDG PET/CT image for a patient with hemorrhagic fever with renal syndrome.
Assuntos
Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Masculino , Humanos , Pessoa de Meia-Idade , Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Rim , FebreRESUMO
The aim of this study was to investigate the antiviral and anti-inflammatory functions of blue light (BL) in cutaneous viral infections. Previously, we examined the photo-biogoverning role of 450 nm BL in SARS-CoV-2-infected cells, which showed that photo-energy could inhibit viral activation depending on the number of photons. However, the communication network between photo-energy irradiation and immune cells involved in viral infections has not been clarified. We verified viral activation, inflammatory responses, and relevant downstream cascades caused by human simplex virus type I (HSV-1) after BL irradiation. To examine the antiviral effect of BL, we further tested whether BL could disturb viral absorption or entry into host cells. The results showed that BL irradiation, but not green light (GL) exposure, specifically decreased plaque-forming activity and viral copy numbers in HSV-1-infected cells. Accumulated BL irradiation inhibited the localization of viral proteins and the RNA expression of characteristic viral genes such as UL19, UL27, and US6, thus exerting to an anti-viral effect. The results also showed that BL exposure during viral absorption interfered with viral entry or destroyed the virus, as assessed by plaque formation and quantitative PCR assays. The levels of the pro-inflammatory mediators interleukin (IL)-18 and IL-1ß in M1-polarized macrophages were increased by HSV-1 infection. However, these increases were attenuated by BL irradiation. Importantly, BL irradiation decreased cGAS and STING expression, as well as downstream NF-κB p65, in M1-polarized HSV-1-infected macrophages, demonstrating anti-viral and anti-inflammatory properties. These findings suggest that BL could serve as an anti-viral and anti-inflammatory therapeutic candidate to treat HSV-1 infections.