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Nontuberculous mycobacterial (NTM) infection is increasing across the world. Although the most common clinical manifestation of NTM disease is lung disease, a rare form of disseminated NTM disease has also been documented. Disseminated NTM usually develops in severely immunocompromised individuals, especially those with advanced AIDS. This manifestation is rare in non-HIV-infected hosts and is associated with immunosuppressed conditions. However, recent reports have suggested that disseminated NTM disease in immunocompetent patients without HIV infection has been increasing. Dissemination may involve any organ system, but a case in the female genital tract has never been reported. We report a case in a 67-yr-old previously healthy woman who presented with a disseminated NTM infection in the uterine cervix. The primary presentation was general fatigue and body weight loss. The patient also presented with a mass formation that mimicked cervical cancer on magnetic resonance imaging. In addition to the cervical mass, the patient presented with a mass formation in the omentum; wall thickening of the vagina, bladder, and ureter; and retention of pleural/peritoneal fluid. Vaginal cytology was negative. A diagnosis was made only after detecting acid-fast bacilli in a biopsy specimen of cervical mass, which was conducted under suspicion of cervical malignancy. Then, Mycobacterium avium was confirmed in a polymerase chain reaction test of cervical tissue. After administration of antimycobacterial therapy, the mass and other findings on magnetic resonance imaging disappeared. Infection in multiple organs leads to the diagnosis of disseminated NTM. This case indicates that, for prompt and accurate diagnosis, efforts to detect specific lesions by an imaging study and to confirm diagnosis pathologically are equally important, especially when local cytology is not convincing. The clinical course of this case may serve as a useful reference in the diagnosis and treatment of NTM.
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Cuello del Útero/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Anciano , Antibióticos Antituberculosos/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
AIMS: To analyze the detailed clinical course of infertile patients with uterine fibroids and to identify optimal and personalized treatment based on the patient or fibroid characteristics. METHODS: Retrospective analysis of a case series was performed on 176 infertile patients with fibroids. The patients were classified into different groups according to different treatments (conservative infertility treatment, myomectomy and non-myomectomy surgery). Patient or fibroid characteristics for different groups were analyzed for a possible correlation with the reproductive outcome. RESULTS: The cumulative pregnancy rates by conservative treatment plateaued in 1 year. Myomectomy improved the reproductive outcome in patients who did not conceive with conservative infertility treatments. The most important determinant of the reproductive outcome in patients by conservative treatment prior to surgery was a past patient history of pregnancy. The most important determinant of the reproductive outcome after myomectomy was patient age. CONCLUSION: Myomectomy should be considered when infertile patients with fibroids do not conceive within 1 year of conservative infertility treatments. The most important determinant of reproductive outcome after myomectomy is patient age. Therefore, for patients younger than 40, the treatment schedule should be carefully considered so that the patients can sufficiently benefit from myomectomy and assisted reproductive technology.
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Infertilidad Femenina/terapia , Leiomioma/terapia , Medicina de Precisión , Neoplasias Uterinas/terapia , Adulto , Factores de Edad , Femenino , Humanos , Leiomioma/patología , Leiomioma/cirugía , Persona de Mediana Edad , Embarazo , Índice de Embarazo , Reproducción , Técnicas Reproductivas Asistidas , Estudios Retrospectivos , Resultado del Tratamiento , Miomectomía Uterina , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugíaRESUMEN
Ovarian teratoid carcinosarcoma involves an epithelial tumor of the Müllerian duct and an immature neuroepithelium, which is a characteristic of immature teratomas. Here, we describe the case of a 60-year-old woman who underwent surgery for a stage IC3 ovarian malignancy. The tumor showed a variety of histological features, including clear cell carcinoma, immature teratoma, and rhabdomyosarcoma, and a PIK3CA mutation was detected at the same locus in each. Two months after surgery and before the start of chemotherapy, multiple bone and liver metastases were found. Four courses of combination therapy with vincristine, actinomycin D and cyclophosphamide, the standard chemotherapy regimen for pediatric rhabdomyosarcoma, were administered, and a complete response was achieved. After a 2-month rest period, the patient developed recurrent peritoneal dissemination and underwent 6 courses of paclitaxel, carboplatin, and bevacizumab chemotherapy, resulting in a partial response. This is the eighth reported case of ovarian teratoid carcinosarcoma. This tumor has a very aggressive course, but initially responds to chemotherapy. However, survival over 5 years has not been reported, and elucidation of the pathogenesis and development of new treatment methods are needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-022-00571-w.
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STUDY DESIGN: A case report and a biomechanical study using a finite element method. OBJECTIVES: To report a case with the cervical spondylolysis and to understand the biomechanics of the cervical spine with spondylolysis at C6. Cervical spondylolysis, although not a common spinal disorder, can occur in athletes. Presently, the exact pathology, natural history and biomechanics are not known. Thus, treatment strategies for this disorder in athletes are in controversy. To treat and/or advise patients with cervical spondylolysis, the cervical spine biomechanics regarding this disorder should be understood. METHODS: A case of a 12-year-old male judo player is presented. The patient presented with occipital and upper neck pain. Plain radiographs, reconstructed CT scan and MRIs of this patient were reviewed. Biomechanically, stress distributions were analyzed in response to 73.6 N axial compression and 1.5-Nm moment in flexion, extension, lateral bending, and axial rotation using a FE model of the intact ligamentous C3 to C7 segment. Bilateral spondylolysis was created in the model at C6. The stress results from the bilateral defect model were compared to the intact model predictions. RESULTS: Plain radiographs showed bilateral C6 spondylolysis, and grade I spondylolisthesis. MRI showed mild disc degeneration at C6/7. With conservative treatment, the symptoms disappeared. In the spondylolysis model, the maximum Von Mises Stresses at C6/7 increased in all cervical spine motions, as compared to the intact case. Specifically, in axial rotation, the stress increase was 3.7-fold as compared to the intact model. The range of motion at C6/7 increased in the spondylolysis model as well. Again, during axial rotation, the increase in motion was 2.3-fold when compared to the intact model. CONCLUSIONS: Cervical spondylolysis can cause biomechanical alterations, especially in axial rotation, leading to increased disc stresses and range of motion. The increased stresses in the disc and the hypermobility would be a dangerous condition for athletes participating in contact sports such as judo. Thus, we recommended that judo players with cervical spondylolysis should change to non-contact sports, such as jogging.
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Vértebras Cervicales/fisiopatología , Artes Marciales , Espondilosis/fisiopatología , Fenómenos Biomecánicos , Vértebras Cervicales/diagnóstico por imagen , Niño , Análisis de Elementos Finitos , Humanos , Masculino , Rango del Movimiento Articular , Espondilosis/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
MRI plays an essential role in patients before treatment for uterine mesenchymal malignancies. Although MRI includes methods such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, the differentiation between uterine myoma and sarcoma always becomes problematic. The present paper discusses important findings to ensure that sarcomas are not overlooked in magnetic resonance (MR) images, and we describe the update in the differentiation between uterine leiomyoma and sarcoma with recent reports.
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BACKGROUND: Because reports on the management of recurrent granulosa cell tumor have been sparse, a consensus as to which patients should undergo surgical resection and which patients should be considered for chemotherapy has not been established. METHODS: A total of 21 tumor recurrences in eight patients with granulosa cell tumor were reviewed. RESULTS: Surgery was performed as the main treatment for 13 recurrences, while chemotherapy was chosen as the main treatment for eight recurrences. Complete tumor resection could be accomplished in 13 of 16 surgeries (81.3%), which include all the ten recurrences without involvement of liver or diaphragm and without ascites. The number of recurrent masses was significantly higher in the early recurrence group (progression free survival < 2 years) than in the late recurrence (progression free survival > 2 years). All cases with a solitary recurrent tumor at an extra-peritoneal site presented a significantly longer progression free survival. CONCLUSIONS: For patients with recurrent granulosa cell tumor, surgery may provide the best disease control. In cases with complete resection, the number of recurrent masses was the predictive factor for the next recurrence, and adjuvant chemotherapy might be considered in such cases.
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Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S) were assessed in association with nutrition and performance status (PS) in Japanese centenarians. Twenty-three centenarians (five men, 18 women) were classified according to their PS 1 (nearly fully ambulatory, n = 2), 2 (in bed less than 50% of daytime, n = 10), 3 (in bed greater than 50%, n = 6), and 4 (completely bedridden, n = 5). Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI), albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin (r = -.694, p < .01), between telomere length and BMI (r = .522, p < .05), between adiponectin and BMI (r = -.574, p < .01), and between DHEA-S and albumin (r = .530, p < .01). When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS (r = -.632, p < .01). It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.
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BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of all pregnancies, and de novo minimal change disease during pregnancy is especially rare. Nephrotic syndrome and, especially, minimal change disease are highly responsive to steroids, and preterm labor may be avoidable if the maternal condition is improved with steroid therapy. Therefore, prompt diagnosis and proper management are critical to maternal and fetal outcome when severe proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese woman presented with systemic edema, oliguria, and severe proteinuria and hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The patient had high urinary protein selectivity. Her illness was diagnosed as de novo nephrotic syndrome with high steroid responsiveness rather than pre-eclampsia. She began steroid pulse therapy the day after admission. Complete remission was confirmed after 3 weeks. The patient did not relapse during pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS In pregnant women with de novo minimal change disease, serious maternal and/or fetal complications may occur if severe proteinuria and hypoalbuminemia are unabated for an extended time. Evaluation of urinary protein selectivity is noninvasive and useful for prediction of steroid responsiveness. Results of urinary protein selectivity can be obtained earlier than results of renal biopsy. Renal biopsy during pregnancy is not always necessary for initiation of steroid therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement of remission and prevent serious perinatal complications.
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Glucocorticoides/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Adulto , Esquema de Medicación , Femenino , Humanos , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificación , EmbarazoRESUMEN
We investigated the direct effects of various bisphosphonates on osteoblasts. At 10(-5) M, clodronate increased alkaline phosphatase activity in cultured MC3T3-E1 (osteoblast-like line) and ST2 (pluripotent mesenchymal line) cells. Etidronate significantly increased alkaline phosphatase activity at 10(-5) M only in MC3T3-E1 cells. These effects were due to an increase in alkaline phosphatase-positive cell numbers, and the differentiation-enhanced cells were capable of mineralization (von Kossa stain). Other bisphosphonates (pamidronate, alendronate, and incadronate) did not increase alkaline phosphatase activity in either cell line. In cultured rat calvariae, clodronate stimulated the expression of genes for alkaline phosphatase and osteocalcin (osteoblast-differentiation markers), but decreased the expression of the gene for tartrate-resistant acid phosphatase (osteoclast marker). Clodronate, etidronate, and incadronate inhibited protein Tyr phosphatase and Ser/Thr phosphatase activities in MC3T3-E1 cells. These data suggest that clodronate acts directly on mesenchymal cells to enhance osteoblast differentiation, and this effect may be partly expressed through inhibition of protein Tyr phosphatase and/or Ser/Thr phosphatase activity.
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Diferenciación Celular/efectos de los fármacos , Ácido Clodrónico/farmacología , Osteoblastos/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Northern Blotting , Diferenciación Celular/genética , Células Cultivadas , Ácido Clodrónico/química , Femenino , Feto , Ratones , Técnicas de Cultivo de Órganos , Osteoblastos/enzimología , Osteoblastos/fisiología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Cráneo/efectos de los fármacos , Cráneo/metabolismo , Células Madre/efectos de los fármacos , Células Madre/enzimología , Células Madre/fisiología , Factores de TiempoRESUMEN
The TGF-ß superfamily comprises pleiotropic cytokines that regulate SMAD and non-SMAD signaling. TGF-ß-SMAD signal transduction is known to be involved in tissue fibrosis, including renal fibrosis. Here, we found that 1,25-dihydroxyvitamin D3-bound [1,25(OH)2D3-bound] vitamin D receptor (VDR) specifically inhibits TGF-ß-SMAD signal transduction through direct interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH)2D3 treatment prevented renal fibrosis through the suppression of TGF-ß-SMAD signal transduction. Based on the structure of the VDR-ligand complex, we generated 2 synthetic ligands. These ligands selectively inhibited TGF-ß-SMAD signal transduction without activating VDR-mediated transcription and significantly attenuated renal fibrosis in mice. These results indicate that 1,25(OH)2D3-dependent suppression of TGF-ß-SMAD signal transduction is independent of VDR-mediated transcriptional activity. In addition, these ligands did not cause hypercalcemia resulting from stimulation of the transcriptional activity of the VDR. Thus, our study provides a new strategy for generating chemical compounds that specifically inhibit TGF-ß-SMAD signal transduction. Since TGF-ß-SMAD signal transduction is reportedly involved in several disorders, our results will aid in the development of new drugs that do not cause detectable adverse effects, such as hypercalcemia.
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Riñón/metabolismo , Riñón/patología , Receptores de Calcitriol/metabolismo , Animales , Calcitriol/análogos & derivados , Calcitriol/metabolismo , Calcitriol/farmacología , Descubrimiento de Drogas , Fibrosis , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Riñón/efectos de los fármacos , Lactamas/farmacología , Ligandos , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Calcitriol/antagonistas & inhibidores , Receptores de Calcitriol/genética , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
Developmentally regulated endothelial cell locus 1 (Del1) is a new angiogenic molecules expressed specifically in early embryonic endothelial cells. We investigated the relationship between Del1 and tumor cell-derived vascular endothelial growth factor (VEGF). Dunn osteosarcoma cells and high- and low-metastatic murine sarcoma cells did not express Del1. However, the expression of Del1 was observed in these primary tumor tissues and the pulmonary metastatic tissues after subcutaneous inoculation in vivo. Every tumor cell-conditioned medium containing VEGF induced the expression of Del1 in murine lung microvascular endothelial (MLE) cells, although control MLE cells did not express Del1. The anti-mouse VEGF monoclonal antibody inhibited the induction of the Del1 expression. In addition, mouse recombinant interleukin-1alpha and tumor necrosis factor-alpha also induced Del1 in MLE cells. Del1 may play an important role in tumor angiogenesis through the effects of tumor-derived factors including VEGF.