RESUMO
BACKGROUND: The global burden of influenza is substantial. It is a major disease that causes annual epidemics and occasionally, pandemics. Given that influenza primarily infects the upper respiratory system, it may be possible to diagnose influenza infection by applying deep learning to pharyngeal images. OBJECTIVE: We aimed to develop a deep learning model to diagnose influenza infection using pharyngeal images and clinical information. METHODS: We recruited patients who visited clinics and hospitals because of influenza-like symptoms. In the training stage, we developed a diagnostic prediction artificial intelligence (AI) model based on deep learning to predict polymerase chain reaction (PCR)-confirmed influenza from pharyngeal images and clinical information. In the validation stage, we assessed the diagnostic performance of the AI model. In additional analysis, we compared the diagnostic performance of the AI model with that of 3 physicians and interpreted the AI model using importance heat maps. RESULTS: We enrolled a total of 7831 patients at 64 hospitals between November 1, 2019, and January 21, 2020, in the training stage and 659 patients (including 196 patients with PCR-confirmed influenza) at 11 hospitals between January 25, 2020, and March 13, 2020, in the validation stage. The area under the receiver operating characteristic curve for the AI model was 0.90 (95% CI 0.87-0.93), and its sensitivity and specificity were 76% (70%-82%) and 88% (85%-91%), respectively, outperforming 3 physicians. In the importance heat maps, the AI model often focused on follicles on the posterior pharyngeal wall. CONCLUSIONS: We developed the first AI model that can accurately diagnose influenza from pharyngeal images, which has the potential to help physicians to make a timely diagnosis.
Assuntos
Aprendizado Profundo , Influenza Humana , Humanos , Inteligência Artificial , Influenza Humana/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Estudos RetrospectivosRESUMO
Stress urinary incontinence (SUI) occurs when abdominal pressure, such as from coughing or sneezing, causes urine leakage. We retrospectively compared tension-free vaginal tape (TVT) and non-ablative vaginal Erbium:YAG laser treatment (VEL) by propensity score (PS) analysis in women with SUI. No PS analysis studies have investigated urethral sling surgery using polypropylene TVT and VEL for SUI. Data from patients aged 35-50 years who were treated for SUI and registered at several institutions were selected. Patients with medical records covering 1 year for the 1-h pad test, who completed the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Overactive Bladder Symptom Score (OABSS), were included. We analyzed 102, 113, and 112 patients in the TVT, VEL, and control groups, respectively. Compared with the control group, the TVT and VEL groups exhibited significant improvement in the 1-h pad test and ICIQ-SF. In the PS analysis, the TVT and VEL groups similarly improved in the 1-h pad test and ICIQ-SF. As for the OABSS, the VEL group showed significantly greater improvement than the TVT group. In the odds ratio analysis for the 1-h pad test, no differences in any of the parameters were observed between TVT and VEL. VEL may be considered an alternative to TVT for SUI treatment.
Assuntos
Lasers de Estado Sólido , Slings Suburetrais , Incontinência Urinária por Estresse , Érbio , Feminino , Humanos , Lasers de Estado Sólido/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgiaRESUMO
BACKGROUND: Neurolymphomatosis (NL) is a rare manifestation of malignant lymphoma that shows selective infiltration to the peripheral nervous system primarily or secondarily. We report a patient with secondary NL caused by germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) who showed selective infiltration of the lumbar plexus to the spinal cord and massive nerve enlargement resulting in severe pain. CASE PRESENTATION: A 72-year-old female exhibited asymmetric motor and sensory impairments and pain in the lower limbs that progressed for five months. Magnetic resonance imaging (MRI) showed an enlarged lumbar plexus, which continued to the cauda equina via the L3 and L4 spinal nerves. Her symptoms gradually worsened. Ten months after the onset of symptoms, the enlarged cauda equina filled the spinal canal space, and the spinal cord was swollen. A cauda equina biopsy was performed, and she was diagnosed with GCB-type DLBCL with CD10 positivity. The primary tumor was found in a mammary cyst. The autopsy study did not show apparent infiltration, except in the nervous system. CONCLUSIONS: Although there are many neurologic phenotypes of malignant lymphoma, the association between the cytological characteristics of lymphoma and the neurological phenotypes is still unclear. Several reports of CD10-positive secondary NL are available, whereas peripheral or central nervous tissue origin lymphoma cases are mostly negative for CD10. CD10 staining may be useful for distinguishing primary NL from secondary NL. NL often has a strong organotropism for peripheral nervous tissue, which makes early diagnosis challenging.
Assuntos
Plexo Lombossacral , Linfoma Difuso de Grandes Células B , Neurolinfomatose , Idoso , Cauda Equina/diagnóstico por imagem , Cauda Equina/patologia , Evolução Fatal , Feminino , Humanos , Plexo Lombossacral/diagnóstico por imagem , Plexo Lombossacral/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética , Neuralgia/etiologia , Neurolinfomatose/secundárioRESUMO
Alveolar soft part sarcoma (ASPS) is a rare malignancy that typically arises in the trunk or extremities and preferentially metastasises to the brain. Radical resection is generally recommended for cranial metastatic ASPS, but stereotactic radiosurgery (SRS) is a recognised alternative for tumours in surgically challenging locations. Here, we present the case of a 22-year-old female, who underwent SRS and systemic therapy with pazopanib for a metastatic ASPS in the left temporal bone. The tumour was successfully controlled without further intervention over 23 months following SRS, which should be considered for metastatic ASPS when surgical resection is not appropriate.
Assuntos
Radiocirurgia , Sarcoma Alveolar de Partes Moles/secundário , Sarcoma Alveolar de Partes Moles/cirurgia , Neoplasias da Base do Crânio/secundário , Neoplasias da Base do Crânio/cirurgia , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Indazóis/uso terapêutico , Pirimidinas/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Neoplasias da Base do Crânio/tratamento farmacológico , Sulfonamidas/uso terapêutico , Osso Temporal , Adulto JovemRESUMO
OBJECTIVES: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion. METHODS: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%. RESULTS: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate. CONCLUSIONS: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.
Assuntos
Equipamentos e Provisões , Hidrogéis , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/instrumentação , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Reto , Tomografia Computadorizada por Raios XRESUMO
A 70-year-old woman experienced pain in both gastrocnemius muscles, numbness in the toes, and muscle weakness in both the legs that lasted for two months. After getting admitted to our hospital, the muscle weakness extended to both her arms, and nerve conduction studies revealed decreased nerve conduction velocity, which was more prominent in the elbow and the axilla than in the wrist. A magnetic resonance imaging revealed a tumor in the right femoral neck, which was histologically diagnosed as plasmacytoma. Laboratory findings revealed IgA lambda type M protein and an elevated VEGF level of 2,320 pg/ml; edema was present in both the legs. After a diagnosis of POEMS syndrome, lenalidomide and dexamethasone treatment were initiated simultaneously, along with irradiation. The treatment improved polyneuropathy, along with a decrease in the VEGF level. Increased vascular permeability due to elevated VEGF led to the development of neuropathy of POEMS syndrome, and treatment against proliferating monoclonal plasma cells is effective. In the present case, we believe that a prompt control of the plasmacytoma with novel therapeutic agents for myeloma with irradiation resulted in the improvement of the neurological symptoms.
Assuntos
Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Síndrome POEMS , Plasmocitoma , Idoso , Feminino , Humanos , Síndrome POEMS/tratamento farmacológico , Fator A de Crescimento do Endotélio VascularRESUMO
A 56-year-old man who sustained a right waist injury 1 month ago, reported to our department complaining of pain in the right waist and femur for 1 day. In a computed tomography examination, hematoma of the right iliopsoas muscle was revealed, and arterial embolization was immediately performed but was not effective. Laboratory findings showed hemoglobin levels as 5.4 g/dl, platelet of 20.2×104/µl, prothrombine time of 13.1 s, partial thromboplastin time (APTT) of 81.1 s, and a convex upward curve of the APTT cross-mixing test. The activity of the coagulation factor VIII was <1.0%, but its amount was 120%, and the level of factor VIII inhibitor was 130 Bethesda Unit/ml. Disseminated intravascular coagulation was not noted. Under the diagnosis of acquired hemophilia A, treatment with prednisolone and recombinant activated factor VII was initiated. However, APTT remained prolonged, and intubation and mechanical ventilation were required because of right hemothorax. After steroid pulse therapy and plasma exchange, APTT returned to its normal range, and the inhibitor disappeared. Thus, we finally succeeded in extubation. This case indicated that intensive care may be necessary in the early phase treatment for acquired hemophilia A.
Assuntos
Hemofilia A/terapia , Troca Plasmática , Respiração Artificial , Fator VIII , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina ParcialRESUMO
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2). METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC). RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen. PD-L1 expression was not significantly correlated with any clinicopathological factor, including progression-free survival and overall survival. The frequency of PD-L1-positive cases was higher in type 2 (36%) than in type 1 (22%) pRCC; however, there was no significant difference in the percentages of score 0 cases (p value = 0.084 in Chi-square test). The frequency of high PD-L1 expression cases was higher in type 2 (23%) than in type 1 (11%), and the frequency of high PD-L1 expression cases was higher in grade 3/4 (21%) than in grade 1/2 (13%). However, no significant association was found between PD-L1 expression and all clinicopathological factors in pRCC. CONCLUSION: High expression of PD-L1 in cancer cells was potentially associated to highly histological grade of malignancy in pRCC. The evaluation of the PD-L1 protein might still be useful for predicting the efficacy of anti-cancer immunotherapy using immuno-checkpoint inhibitors, however, not be useful for predicting the clinical prognosis.
Assuntos
Antígeno B7-H1/biossíntese , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Idoso , Carcinoma de Células Renais/diagnóstico , Feminino , Humanos , Neoplasias Renais/diagnóstico , Masculino , Estudos RetrospectivosRESUMO
The RCC-SELECT study showed the correlation between single nucleotide polymorphisms (SNP) in STAT3 gene and survival in metastatic renal cell carcinoma (mRCC) patients with first-line interferon-α (IFN-α). In that study, even patients with STAT3 SNP linked to shorter overall survival (OS) exhibited remarkably improved prognosis. All 180 patients evaluated in the above study were further analyzed for correlation between OS and demographics/clinicopathological parameters. OS was estimated using the Kaplan-Meier method. Associations between OS and potential prognostic factors were assessed using the log-rank test and the Cox proportional hazards model. The median OS was 42.8 months. Univariate analysis showed that worse Eastern Cooperative Oncology Group-performance status (ECOG-PS), high T stage, regional lymph node metastasis, distant metastasis, higher grade, infiltrative growth pattern, the presence of microscopic vascular invasion (MVI), hypercalcemia, anemia, thrombocytopenia and elevated C-reactive protein were significantly associated with OS. Multivariate analysis revealed that ECOG-PS (hazard ratio [HR] = 3.665, P = 0.0004), hypercalcemia (HR = 6.428, P = 0.0005) and the presence of MVI (HR = 2.668, P = 0.0109) were jointly significant poor prognostic factors. This is the first study analysing prognostic factors of mRCC patients with first-line IFN-α using large cohort of the prospective study. The present study suggests that first-line IFN-α is still a useful therapy for mRCC even in the era of molecular targeted therapy.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fator de Transcrição STAT3/genética , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Cancer stem-like cells (CSC) or cancer-initiating cells are now considered to be an important cell population related to cancer recurrence and the resistance to anti-cancer therapy. Tumor-associated macrophages (TAM) are a main component of stromal cells and are related to cancer progression in clear cell renal cell carcinoma (ccRCC). Because the detailed mechanisms allowing the maintenance of CSC in cancer tissues remain unclear, we investigated the relationship between TAM and CD44-expressing cancer cells in ccRCC. CD44 was used as a marker for CSC, and CD163 and CD204 were used as markers for TAM. CD44-positive cancer cells were detected in 37 of the 103 cases. Although statistical analysis showed no relationship between CD44-positive cancer cells and the clinical course, the distribution of CD44-positive cancer cells was significantly associated with a high density of TAM. Our in vitro study using RCC cell lines and human macrophages demonstrated that CD44 expression was upregulated by direct co-culture with macrophages. Silencing of TNF-alpha on macrophages abrogated the upregulation of CD44 expression in cancer cells. Macrophage-induced CD44 overexpression was also suppressed by NF-κB inhibitors. These results suggest that TNF-alpha derived from TAM is linked to CD44 overexpression via NF-κB signaling in ccRCC.
Assuntos
Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Receptores de Hialuronatos/metabolismo , Neoplasias Renais/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: Mutations of the inverted formin 2 gene (INF2), which encodes a member of the formin family, cause autosomal dominant focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) disease-associated FSGS. However, their role in idiopathic FSGS remains unclear. This study investigated INF2 localization in the normal adult kidney and its expression in children with idiopathic nephrotic syndrome. METHODS: We generated a rabbit polyclonal antibody against the conjugated peptide from human INF2 and studied the glomerular expression of INF2 and synaptopodin using normal human adult kidney tissues and tissues from children with glomerular diseases such as minimal change disease (MCD), FSGS, IgA nephropathy (IgAN), non-IgA mesangial proliferative glomerulonephritis (non-IgAN), and Henoch-Schönlein purpura nephritis (HSPN). RESULTS: The anti-INF2 antibody detected an approximately 140-kD fragment isolated from adult mature glomeruli by western blotting. Immunohistochemically, INF2 was detected in podocytes and renal arteries. Among 56 patients, INF2 in glomeruli was expressed at a similar level in patients with MCD, IgAN, non-IgAN, or HSPN and controls. In FSGS patients, INF2 expression in glomeruli was either decreased or absent. There was a relationship between decreased INF2 expression and the clinical severity of steroid resistant nephrotic syndrome (SRNS). CONCLUSION: We propose that examination of INF2 expression may help to differentiate MCD from FSGS and evaluate the clinical severity of SRNS in children.
Assuntos
Glomerulosclerose Segmentar e Focal/metabolismo , Glomérulos Renais/química , Proteínas dos Microfilamentos/análise , Nefrose Lipoide/metabolismo , Síndrome Nefrótica/congênito , Adolescente , Fatores Etários , Biomarcadores/análise , Biópsia , Western Blotting , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Regulação para Baixo , Feminino , Forminas , Glomerulosclerose Segmentar e Focal/diagnóstico , Humanos , Imuno-Histoquímica , Lactente , Glomérulos Renais/patologia , Masculino , Nefrose Lipoide/diagnóstico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/metabolismo , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC). METHODS: We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA. RESULTS: Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically >60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (<60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival. CONCLUSION: In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous.
Assuntos
Carcinoma/metabolismo , Carcinoma/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/virologia , Infecções por Papillomavirus/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Infecções por Papillomavirus/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) . METHOD: VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. RESULTS AND DISCUSSION: Without division, dose differences between cumulative distribution and plan were not significant. In the condition where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. CONCLUSION: The present method was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR.
Assuntos
Radiometria/métodos , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Humanos , Imagens de Fantasmas , Radiocirurgia/métodos , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Although concurrent chemoradiotherapy (CCRT) has become the standard approach for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), most patients are not candidates for this treatment because of comorbidities. We evaluated the safety and efficacy of carbon ion radiotherapy (CIRT) in LA-NSCLC patients. METHODS: Patients with stage IIA to IIIA (UICC 7th edition) LA-NSCLC were enrolled in a sequential phase I/II trial. For a phase I dose escalation study, the total prescribed dose was increased by 4 Gray equivalents (GyE) in 2 steps, from 68 to 72 GyE and then to 76 GyE, using 16 fractions over 4 weeks. After determining the recommended dose, the phase II trial was started in an expanded cohort. RESULTS: Of the 36 patients treated in phase I, 2 grade 3 adverse events (radiation pneumonitis and tracheoesophageal fistula) were observed in the 76 GyE group. Accordingly, for phase II, the next consecutive 26 patients were treated with 72 GyE, with no grade 3 to 5 toxicities resulting. A total of 62 eligible patients were recruited. The majority of patients (49 of 62) were N0 or N1 patients, and the rest (13 of 62) were single-station N2 patients. The median follow-up period was 25.2 months. The 2-year local control rate (LCR) and overall survival (OS) for the entire cohort were 93.1% and 51.9%, respectively. In particular, patients with cT3-4N0 had an excellent prognosis; the 2-year OS and LCR were 69.3% and 100%, respectively. CONCLUSIONS: Short-course CIRT monotherapy shows promise as an effective nonsurgical treatment for inoperable LA-NSCLC.
Assuntos
Carbono/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia com Íons Pesados/efeitos adversos , Íons Pesados/efeitos adversos , Neoplasias Pulmonares/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Serelaxin, a recombinant form of human relaxin-2, is in development for treating acute heart failure (AHF) and a Phase II study in Japanese AHF patients was conducted. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled study of serelaxin at 10 and 30 µg·kg(-1)·day(-1)continuous intravenous infusion for up to 48 h, added to standard care for Japanese AHF patients. Primary endpoints were adverse events (AEs) through Day 5, serious AEs (SAEs) through Day 14, and serelaxin pharmacokinetics. Secondary endpoints included changes in systolic blood pressure (SBP) and cardiorenal biomarkers. A total of 46 patients received the study drug and were followed for 60 days. The observed AE profile was comparable between the groups, with no AEs of concern. Dose-dependent increase in the serum concentration of serelaxin was observed across the 2 dose rates of serelaxin. A greater reduction in SBP was observed with serelaxin 30 µg·kg(-1)·day(-1)vs. placebo (-7.7 [-16.4, 1.0] mmHg). A greater reduction in NT-proBNP was noted with serelaxin (-50.8% and -54.9% for 10 and 30 µg·kg(-1)·day(-1), respectively at Day 2). CONCLUSIONS: Serelaxin was well tolerated in this study with Japanese AHF patients, with no AEs of concern and favorable beneficial trends on efficacy. These findings support further evaluation of serelaxin 30 µg·kg(-1)·day(-1)in this patient population.
Assuntos
Povo Asiático , Insuficiência Cardíaca/tratamento farmacológico , Relaxina/uso terapêutico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Comorbidade , Método Duplo-Cego , Quimioterapia Combinada , Dispneia/etiologia , Dispneia/prevenção & controle , Feminino , Insuficiência Cardíaca/complicações , Humanos , Infusões Intravenosas , Japão , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Relaxina/efeitos adversos , Relaxina/sangue , Relaxina/farmacocinética , Resultado do TratamentoRESUMO
A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 ± 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo.
Assuntos
Óxidos N-Cíclicos , Diagnóstico por Imagem/métodos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Neoplasias Mamárias Experimentais/química , Marcadores de Spin , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Óxidos N-Cíclicos/síntese química , Óxidos N-Cíclicos/farmacologia , Elétrons , Feminino , Glutationa/química , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Mamárias Experimentais/diagnóstico , Camundongos , Camundongos Endogâmicos C57BL , Imagens de Fantasmas , Prótons , Marcadores de Spin/síntese química , Água/químicaRESUMO
BACKGROUND: Gray leaf spot (GLS), caused by Magnaporthe oryzae (anamorph Pyricularia oryzae), in ryegrasses is a very serious problem. Heavily infected small seedlings die within a matter of days, and stands of the grasses are seriously damaged by the disease. Thus, the development of GLS-resistant cultivars has become a concern in ryegrass breeding. RESULTS: Phenotypic segregations in a single cross-derived F1 population of Italian ryegrass (Lolium multiflorum Lam.) indicated that the GLS resistance in the population was possibly controlled by one or two dominant genes with 66.5-77.9% of broad-sense heritability. In bulked segregant analyses, two simple sequence repeat (SSR) markers, which have so far been reported to locate on linkage group (LG) 3 of Italian ryegrass, showed specific signals in the resistant parent and resistant bulk, indicating that the resistance gene locus was possibly in the LG 3. We thus constructed a genetic linkage map of the LG 3 covering 133.6 centimorgan with other SSR markers of the LG 3 of Italian ryegrass and grass anchor probes that have previously been assigned to LG 3 of ryegrasses, and with rice expressed sequence tag (EST)-derived markers selected from a rice EST map of chromosome (Chr) 1 since LG 3 of ryegrasses are syntenic to rice Chr 1. Quantitative trait locus (QTL) analysis with the genetic linkage map and phenotypic data of the F1 population detected a major locus for GLS resistance. Proportions of phenotypic variance explained by the QTL at the highest logarithm of odds scores were 61.0-69.5%. CONCLUSIONS: A resistance locus was confirmed as novel for GLS resistance, because its genetic position was different from other known loci for GLS resistance. Broad-sense heritability and the proportion of phenotypic variance explained by the QTL were similar, suggesting that most of the genetic factors for the resistance phenotype against GLS in the F1 population can be explained by a function of the single resistance locus. We designated the putative gene for the novel resistance locus as LmPi2. LmPi2 will be useful for future development of GLS-resistant cultivars in combination with other resistance genes.
Assuntos
Resistência à Doença , Lolium/genética , Magnaporthe/fisiologia , Doenças das Plantas/imunologia , Locos de Características Quantitativas/genética , Cruzamento , Mapeamento Cromossômico , Etiquetas de Sequências Expressas , Ligação Genética , Lolium/imunologia , Lolium/microbiologia , Repetições de Microssatélites/genética , Fenótipo , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Plântula/genética , Plântula/imunologia , Plântula/microbiologia , SinteniaRESUMO
Variable Radio Frequency Proton-Electron Double-Resonance Imaging (VRF PEDRI) enables extracting a functional map from a limited number of images acquired at pre-selected EPR frequencies using specifically designed paramagnetic probes with high quality spatial resolution and short acquisition times. In this work we explored potential of VRF PEDRI for pH mapping of aqueous samples using recently synthesized pH-sensitive phosphonated trityl radical, pTR. The ratio of Overhauser enhancements measured at each pixel at two different excitation frequencies corresponding to the resonances of protonated and deprotonated forms of pTR probe allows for a pH map extraction. Long relaxation times of pTR allow for pH mapping at EPR irradiation power as low as 1.25 W during 130 s acquisition time with spatial resolution of about 1 mm. This is particularly important for in vivo applications enabling one to avoid sample overheating by reducing RF power deposition.
RESUMO
In a previous study, heat-treated noradrenaline induced flowering of the short-day plant Lemna paucicostata Hegelmaier 151. In the present study, we found that heat-treated noradrenaline also had flower-inducing activity in short-day L. paucicostata strains 441 and 6746 and in long-day L. gibba strain G3. The flower-inducing activity in these plants was enhanced by water homogenates of eggplant (Solanum melongena L.).
Assuntos
Araceae/efeitos dos fármacos , Araceae/crescimento & desenvolvimento , Flores/efeitos dos fármacos , Flores/crescimento & desenvolvimento , Temperatura Alta , Norepinefrina/farmacologia , Fatores de TempoRESUMO
We report a 40-year-old woman diagnosed as having acute myeloid leukemia with CBFB-MYH11. Before and after stem cell transplantation in the phase of molecular remission of the marrow, CBFB-MYH11-positive cells were detected by RT-PCR analysis in skin lesions. The former was pathologically diagnosed as leukemic infiltration, while the latter was considered to be graft-versus-host disease. We can speculate that a low level of leukemic stem cells not detectable by RT-PCR analysis remained in the bone marrow, at least prior to transplantation. This case may suggest interesting biological features of inv(16)-type acute myeloid leukemia.