RESUMO
Craniopharyngiomas are tumors that arise from the remnants of Rathke's pouch along the nasopharynx to the diencephalon. Current standard of care includes maximal surgical resection versus adjuvant radiation if a maximal resection is unfeasible. Pharmacological therapy with MAPK targeted agents is an emerging therapeutic option for tumors with BRAF V600E mutations. We report a 45-year-old male with a strictly third ventricle papillary craniopharyngioma with a BRAF V600E mutation. After initial surgery with subtotal resection, the patient demonstrated durable response to targeted BRAF and MEK inhibitor therapy with vemurafenib and cobimetinib. Our report suggests that targeted therapy may reduce the need for radiation and impact surgical interventions in select cases.
Assuntos
Azetidinas , Craniofaringioma , Piperidinas , Neoplasias Hipofisárias , Masculino , Humanos , Pessoa de Meia-Idade , Vemurafenib/uso terapêutico , Craniofaringioma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Mutação/genéticaRESUMO
Challenges in identifying a glioblastoma's infiltrative edge during neurosurgical procedures result in rapid recurrence. A label-free fluorescence lifetime imaging (FLIm) device was used to evaluate glioblastoma's infiltrative edge in vivo in 15 patients (89 samples). FLIm data were analyzed according to tumor cell density, infiltrating tissue type (gray and white matter), and diagnosis history (new or recurrent). Infiltrations in white matter from new glioblastomas showed decreasing lifetimes and a spectral red shift with increasing tumor cell density. Areas of high versus low tumor cell density were separated through a linear discriminant analysis with a ROC-AUC=0.74. Current results support the feasibility of intraoperative FLIm for real-time in vivo brain measurements and encourage refinement to predict glioblastoma infiltrative edge, underscoring the ability of FLIm to optimize neurosurgical outcomes.
RESUMO
Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular aspects have been published; however, these were not complemented with ultrastructural evidence. Our ultrastructural examination of glioma vessels reveals several unique and critical features related to their mechanisms of progression and metastasis strategy. The detailed ultrastructural survey of 18 isocitrate dehydrogenase-wildtype (IDH1-wt) glioblastomas and 12 isocitrate dehydrogenase-mutant (IDH1-mt) High-grade gliomas indicated that tumor vessels of both types had undergone deformities such as the thickening of the vessel wall (VW) and proliferation of the basement membrane, contour distortions, abnormal and discontinuous basal lamina, tumor cells' invasion and colonization of VW, disappearance of endothelial cells (ECs), pericytes, and smooth muscle cells, as well as the formation of a continuous ring of tumor cells attached to the luminal side of VW in numerous cases. The latter feature is a clear sign of vascular mimicry (VM) that was previously suggested in gliomas but never shown by TEM. Additionally, the vascular invasion was carried out by a large number of tumor cells and was accompanied by the accumulation of tumor lipids in the vessels' lumina and VWs; these two features are distinct for gliomas and may alter the course of the clinical presentation and overall prognosis. This raises the issue of how to specifically target tumor cells involved in vascular invasion in order to optimize prognosis and overcome these mechanisms employed by the tumor cells.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico , Glioblastoma/patologia , Isocitrato Desidrogenase/genética , Células Endoteliais/patologia , Astrocitoma/patologia , Glioma/patologia , Neoplasias Encefálicas/patologia , MutaçãoRESUMO
Aim: H3G34 diffuse hemispheric glioma is a CNS tumor that is difficult to diagnose and treat and accompanied with poor prognosis. It is becoming clear that extra CNS metastasis may present in a subset of patients with H3G34 gliomas, further complicating diagnosis and treatment. Materials & methods: We present a case of a 19-year-old female with a H3G34 mutant diffuse hemispheric glioma with osseous metastases. We then provide a literature review of the most recent understanding of H3G34 mutant malignancies. Conclusion: Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate diagnostic methodologies and targeted therapeutic approaches.
Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Feminino , Humanos , Adulto Jovem , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologiaRESUMO
Gliomas are the most common malignant brain tumors with poor prognosis. The WHO's classification recognizes isocitrate dehydrogenase 1 (IDH1) mutant astrocytoma and IDH1-wildtype glioblastoma (GBM). The IDH1 mutation confers a survival advantage over the wildtype. There are several explanations for the metabolic advantage of the IDH1 mutation, some involve mitochondrial implications. Since an ultrastructural comparison of both tumor genotypes is still lacking, we surveyed the ultrastructural effects of the IDH1 mutation on the mitochondria of the IDH1-mutant astrocytoma (n = 15) and IDH1-wildtype glioblastoma (n = 15) tumors. Our results show that both IDH1 genotypes have degenerate and uncoupled mitochondria; this has not been reported before. The presence of ample lipid inclusions and lipid droplets in the cytoplasm of both genotypes support our conclusion of dysfunctional uncoupled mitochondria. Thus, the IDH1 mutation may have no ultrastructural consequences on the mitochondria, and the aberrant mitochondria in both genotypes may be the result of other unknown mutations. The status of the mitochondria in these genotypes portends a clinical challenge since tumor cells with uncoupled mitochondria are more primitive, aggressive, and considerably treatment resistant.
RESUMO
We here characterize changes in metabolite patterns in glioblastoma patients undergoing surgery and concurrent chemoradiation using machine learning (ML) algorithms to characterize metabolic changes during different stages of the treatment protocol. We examined 105 plasma specimens (before surgery, 2 days after surgical resection, before starting concurrent chemoradiation, and immediately after chemoradiation) from 36 patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma. Untargeted GC-TOF mass spectrometry-based metabolomics was used given its superiority in identifying and quantitating small metabolites; this yielded 157 structurally identified metabolites. Using Multinomial Logistic Regression (MLR) and GradientBoostingClassifier (GB Classifier), ML models classified specimens based on metabolic changes. The classification performance of these models was evaluated using performance metrics and area under the curve (AUC) scores. Comparing post-radiation to pre-radiation showed increased levels of 15 metabolites: glycine, serine, threonine, oxoproline, 6-deoxyglucose, gluconic acid, glycerol-alpha-phosphate, ethanolamine, propyleneglycol, triethanolamine, xylitol, succinic acid, arachidonic acid, linoleic acid, and fumaric acid. After chemoradiation, a significant decrease was detected in 3-aminopiperidine 2,6-dione. An MLR classification of the treatment phases was performed with 78% accuracy and 75% precision (AUC = 0.89). The alternative GB Classifier algorithm achieved 75% accuracy and 77% precision (AUC = 0.91). Finally, we investigated specific patterns for metabolite changes in highly correlated metabolites. We identified metabolites with characteristic changing patterns between pre-surgery and post-surgery and post-radiation samples. To the best of our knowledge, this is the first study to describe blood metabolic signatures using ML algorithms during different treatment phases in patients with glioblastoma. A larger study is needed to validate the results and the potential application of this algorithm for the characterization of treatment responses.
RESUMO
Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular aspects have been published; however, these were not complemented with ultrastructural evidence. Our ultrastructural examination of glioma vessels reveals several unique and critical features related to their mechanisms of progression and metastasis strategy. The detailed ultrastructural survey of 18 IDH1 -wildtype glioblastomas (GBM) and 12 IDH1 -mutant High-grade gliomas indicated that tumor vessels of both types had undergone deformities such as the thickening of the vessel wall (VW) and proliferation of the basement membrane, contour distortions, abnormal and discontinuous basal lamina, tumor cells' invasion and colonization of VW, disappearance of endothelial cells (ECs), pericytes, and smooth muscle cells, as well as the formation of a continuous ring of tumor cells attached to the luminal side of VW in numerous cases. The latter feature is a clear sign of vascular mimicry (VM) that was previously suggested in gliomas but never shown by TEM. Additionally, the vascular invasion was carried out by a large number of tumor cells and was accompanied by the accumulation of tumor lipids in the vessels' lumina and VWs; these two features are distinct for gliomas and may alter the course of the clinical presentation and overall prognosis. This raises the issue of how to specifically target tumor cells involved in vascular invasion in order to optimize prognosis and overcome these mechanisms employed by the tumor cells.
RESUMO
Identifying isocitrate dehydrogenase (IDH)-mutation and glioma subtype during surgery instead of days later can aid in modifying tumor resection strategies for better survival outcomes. We report intraoperative identification of IDH-mutant glioma (N = 12 patients) with a clinically compatible fluorescence lifetime imaging (FLIm) device (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm). The fluorescence-derived parameters were analyzed to study the optical contrast between IDH-mutant tumors and surrounding brain tissue. IDH-mutant oligodendrogliomas exhibited shorter lifetimes (3.3 ± 0.1 ns) than IDH-mutant astrocytomas (4.1 ± 0.1 ns). Both IDH-mutant glioma subtypes had shorter lifetimes than white matter (4.6 ± 0.4 ns) but had comparable lifetimes to cortex. Lifetimes also increased with malignancy grade within IDH-mutant oligodendrogliomas (grade 2: 2.96 ± 0.08 ns, grade 3: 3.4 ± 0.3 ns) but not within IDH-mutant astrocytomas. The current results support the feasibility of FLIm as a surgical adjuvant for identifying IDH-mutant glioma tissue.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Oligodendroglioma/cirurgia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Fluorescência , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/cirurgia , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Astrocitoma/cirurgia , Mutação/genéticaRESUMO
Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n = 18) and IDH1 mutant (IDH1-mt) astrocytoma (n = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals.
RESUMO
Steel is one of the most basic ingredients, which plays an important role in the machinery industry. However, the steel surface defects heavily affect its quality. The demand for surface defect detectors draws much attention from researchers all over the world. However, there are still some drawbacks, e.g., the dataset is limited accessible or small-scale public, and related works focus on developing models but do not deeply take into account real-time applications. In this paper, we investigate the feasibility of applying stage-of-the-art deep learning methods based on YOLO models as real-time steel surface defect detectors. Particularly, we compare the performance of YOLOv5, YOLOX, and YOLOv7 while training them with a small-scale open-source NEU-DET dataset on GPU RTX 2080. From the experiment results, YOLOX-s achieves the best accuracy of 89.6% mAP on the NEU-DET dataset. Then, we deploy the weights of trained YOLO models on Nvidia devices to evaluate their real-time performance. Our experiments devices consist of Nvidia Jetson Nano and Jetson Xavier AGX. We also apply some real-time optimization techniques (i.e., exporting to TensorRT, lowering the precision to FP16 or INT8 and reducing the input image size to 320 × 320) to reduce detection speed (fps), thus also reducing the mAP accuracy.
Assuntos
Indústrias , Pesquisadores , Humanos , Aço , Aprendizado de MáquinaRESUMO
The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.
RESUMO
Progressive multifocal leucoencephalopathy (PML) is a demyelinating white matter disease that most often affects immunocompromised people infected by JC virus. The diagnostic gold standard is demonstrable viral DNA or protein from histopathological tissue. However, there are few detailed descriptions of cortical grey matter involvement on neuroimaging. Here we describe the histopathological correlate of cerebral grey matter involvement and radiological accompaniment in a patient with biopsy proven PML.
Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Adulto , DNA Viral , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/complicações , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Neuroimagem , Adulto JovemRESUMO
PURPOSE: This study investigated the outcomes of pullout fixation for medial meniscus posterior root tears (MMPRTs) in patients ≤ 60 years old versus patients > 60 years old. It was hypothesized that older patients would demonstrate results comparable with those of younger patients. METHODS: Patients with pullout fixation who were followed-up for more than 5 years were included. Patients were categorized into two groups based on age (group A, ≤ 60 years; group B, > 60 years). The Lysholm score, Kellgren-Lawrence (K-L, 0/1/2/3/4) grade, and medial joint space width were evaluated retrospectively. Preoperative results were compared with the final results in each group, which were compared between groups. RESULTS: Twenty-five patients in group A (mean age, 54.7 ± 3.8 years) and 22 patients in group B (mean age, 65.6 ± 4.4 years) were recruited. The mean follow-up duration was 70.9 months. The Lysholm score (group A, 53.0 ± 9.1 to 86.0 ± 12.1, P < 0.001; group B, 51.1 ± 7.1 to 82.9 ± 9.7, P < 0.001) improved significantly. However, the joint space width (group A, 4.7 ± 1.1 to 3.9 ± 1.1 mm, P < 0.001; group B, 4.7 ± 0.9 to 3.8 ± 0.9 mm, P < 0.001) and K-L grade (group A, 3/17/5/0/0 to 0/7/11/7/0, P < 0.001; group B, 2/14/6/0/0 to 0/3/14/5/0, P < 0.001) worsened significantly. No significant differences between groups were observed in final outcomes, including Lysholm score (n.s.), K-L grade (n.s.), and joint space narrowing (n.s.). No case with operation failure that require total knee arthroplasty was not observed. CONCLUSION: MMPRT fixation did not prevent the progression of arthrosis completely. However, clinical outcomes were not age-dependent. Thus, age may not be a critical factor to consider when applying fixation. LEVEL OF EVIDENCE: Retrospective case-control study; Level of evidence, IV.
Assuntos
Progressão da Doença , Osteoartrite do Joelho/fisiopatologia , Lesões do Menisco Tibial/fisiopatologia , Lesões do Menisco Tibial/cirurgia , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Escore de Lysholm para Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/prevenção & controle , Estudos RetrospectivosRESUMO
BACKGROUND: Whole slide imaging (WSI) finds increasingly higher value in everyday surgical pathology in addition to its well-established use for educational and research purposes. However, its diagnostic utility, especially in subspecialty settings such as neuropathology, is not fully validated. Neuropathology practice is unique with smaller overall tissue size and frequent need for high-power evaluation. In addition, tumor grade is an integral part of the initial diagnosis. The purpose of this study is to assess the feasibility of primary pathology diagnosis of surgical neuropathology specimens using WSI. MATERIALS AND METHODS: We reviewed consecutive surgical neuropathology cases diagnosed in our institution during a 2-month period and identified a single diagnostic slide, which was scanned at 40× magnification. Two neuropathologists who were blinded to the original diagnoses reviewed the whole slide image and rendered a diagnosis including tumor grade when applicable. They reviewed the single diagnostic slide after a wash-out period. Intra- and inter-observer discrepancies, as well as reasons for discrepancies, were evaluated. RESULTS: The concordance rates were 94.9% and 88% for two neuropathologists. Two critical issues leading to discrepancies were identified: (1) identification of mitoses and (2) recognition of nuclear details. CONCLUSIONS: Given the current study is exclusively for surgical neuropathology cases, an all-encompassing conclusion about the utility of WSI for diagnostic purposes may not be available. Nevertheless, pathologists should be aware of the potential pitfalls due to identification of mitotic figures and nuclear details. We recommend independent validation for each subspecialty of pathology to identify subspecialty-specific concerns, so they can be properly addressed.
RESUMO
OBJECTIVE: Oligodendrogliomas are rare in the pediatric population, and most oligodendroglioma-like tumors in this age group may belong to other entities. In addition, accurate diagnosis and grading of such lesions using criteria developed for adult oligodendrogliomas prove difficult, and often controversial. MATERIAL AND METHOD: During a study of tumors previously diagnosed as pediatric oligodendroglioma, we identified four tumors displayed features of that resembled oligodendroglioma, angiocentric glioma and dysembryoplastic neuroepithelial tumor but could not be classified as either one of these entities. Ther clinical, histological and immunohistochemical features of these cases were investigated in this study. RESULTS: Two male (both 9 years old) and two female (ages 4 years and 20 months) patients presented with new onset of seizures. All patients were treated surgically, and two required reoperation. Histologically, the tumors were well-differentiated glial neoplasms with focal angiocentric pattern, delicate vascularity, diffuse growth, infiltrative margins, cortical nodules, focal myxoid areas, and leptomeningeal extension. Immunohistochemical studies showed diffuse nuclear positivity with Olig-2 and GFAP antibodies, whereas staining with neuronal markers, EMA, p53, and IDH1 were negative. Fluorescent in-situ hybridization analysis demonstrated intact 1p/19q in all tumors, and there was no ultrastructural evidence of ependymal differentiation. All patients were alive with disease with a mean follow-up of 112 months. CONCLUSION: These four cases illustrate the morphological diversity of well-differentiated, oligodendroglioma-like glial neoplasms and the uncertainty in their classification among pediatric tumors.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/patologia , Neuroglia/patologia , Oligodendroglioma/patologia , Teratoma/patologia , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Diferenciação Celular , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Neoplasias Neuroepiteliomatosas/química , Neoplasias Neuroepiteliomatosas/classificação , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/cirurgia , Neuroglia/química , Procedimentos Neurocirúrgicos , Oligodendroglioma/química , Oligodendroglioma/classificação , Oligodendroglioma/complicações , Oligodendroglioma/cirurgia , Valor Preditivo dos Testes , Reoperação , Convulsões/etiologia , Teratoma/química , Teratoma/classificação , Teratoma/complicações , Teratoma/cirurgia , Resultado do TratamentoRESUMO
There is increasing attention to medical problems of musicians. Many studies find a high prevalence of work-related musculoskeletal disorders in musicians, ranging from 73.4% to 87.7%, and string players have the highest prevalence of musculoskeletal problems. This paper examines the various positions and movements of the upper extremities in string players: 1) basic postures for holding instruments, 2) movements of left upper extremity: fingering, forearm posture, high position and vibrato, 3) movements of right upper extremity: bowing, bow angles, pizzicato and other bowing techniques. These isotonic and isometric movements can lead to musculoskeletal problems in musicians. We reviewed orthopedic disorders that are specific to string players: overuse syndrome, muscle-tendon syndrome, focal dystonia, hypermobility syndrome, and compressive neuropathy. Symptoms, interrelationships with musical performances, diagnosis and treatment of these problems were then discussed.
Assuntos
Transtornos Traumáticos Cumulativos/etiologia , Doenças Musculoesqueléticas/etiologia , Música , Doenças Profissionais/etiologia , Humanos , Doenças NeuromuscularesRESUMO
Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry-based restriction fragment mass polymorphism (RFMP) assay was adapted to human papillomavirus (HPV) genotyping. The analytical sensitivity and the clinical utility were evaluated by testing defined HPV genome equivalents and a total of 426 specimens composed of normal cytology, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and invasive squamous cell carcinoma. The RFMP assay was able to detect 38.4-114.6 genomic equivalents of a wide variety of HPV types. The RFMP assay detected 34 different HPV genotypes in cervical samples of which 8% were found to be multiple-type infections. The high-risk HPV positivity rate according to the histological diagnosis was 7.9% (8/101), 31.7% (38/120), 50% (55/110), 86% (37/43), 96.2% (50/52) in normal, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and squamous cell carcinoma subgroups, respectively. Diagnostic sensitivities/specificities for the cervical lesions of squamous cell carcinoma and high grade squamous intraepithelial lesion or worse histology were found to be 96.2%/92.1% and 91.6%/92.1%, respectively. The sensitivity, accuracy, wide range of genotype identification and high-throughput capacity with cost-effectiveness of the test consumables make the RFMP assay suitable for mass screening and monitoring of HPV-associated cervical cancer.
Assuntos
Tipagem Molecular , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Sequência de Bases , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colo do Útero/patologia , Colo do Útero/virologia , DNA Viral , Feminino , Genótipo , Humanos , Programas de Rastreamento , Polimorfismo Genético , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Mycobacteruim kansasii occasionally causes disseminated infection with poor outcome in immunocompromised patients. We report the first case of disseminated M. kansasii infection associated with multiple skin lesions in a 48-yr-old male with myelodysplastic syndrome. The patient continuously had taken glucocorticoid during 21 months and had multiple skin lesions developed before 9 months without complete resolution until admission. Skin and mediastinoscopic paratracheal lymph node (LN) biopsies showed necrotizing granuloma with many acid-fast bacilli. M. kansasii was cultured from skin, sputum, and paratracheal LNs. The patient had been treated successfully with isoniazid, rifampin, ethmabutol, and clarithromycin, but died due to small bowel obstruction. Our case emphasizes that chronic skin lesions can lead to severe, disseminated M. kansasii infection in an immunocompromised patient. All available cases of disseminated M. kansasii infection in non HIV-infected patients reported since 1953 are comprehensively reviewed.
Assuntos
Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium kansasii , Dermatopatias Bacterianas/diagnóstico , Antituberculosos/uso terapêutico , Claritromicina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/imunologia , Mycobacterium kansasii/isolamento & purificação , Síndromes Mielodisplásicas/tratamento farmacológico , Rifampina/uso terapêutico , Dermatopatias Bacterianas/imunologia , Dermatopatias Bacterianas/patologia , Escarro/microbiologia , Síndrome de Sweet/diagnósticoRESUMO
AIM OF STUDY: This study was performed to elicit the effectiveness of bee venom (BV), a traditional immunosuppressive Korean acupuncture agent, on the maturation of dendrtic cells (DCs). MATERIALS AND METHODS: Immature dendritic cells (iDCs) were generated from mouse bone marrow cells with GM-CSF. After 10 days of initial differentiation, DCs were activated with lipopolysaccharides (LPS) for another 48h in the presence or absence of BV. Surface molecule analysis, intracytoplasmic staining of cytokines, FITC-conjugated antigen uptake, and transwell migration assays were conducted with iDCs and activated DCs. RESULTS: Up-regulation of costimulatory molecules, typical of mature DCs (mDCs) was inhibited by addition of BV. Pro-inflammatory cytokines were also found to be reduced with BV treatment in LPS-stimulated DC. A decrease in antigen uptake upon the maturation of DC was reversed in low dose BV treated mDC. In addition, BV treated mDC demonstrated reduced directional migration in response to CCL21, a lymphoid chemokine which directs mDC. CONCLUSIONS: BV may have a therapeutic effect an on abnormally activated immune status, such as autoimmune rheumatoid arthritis, through an immune-modulatory effect on DC.
Assuntos
Antígenos CD/efeitos dos fármacos , Venenos de Abelha/farmacologia , Células Dendríticas/efeitos dos fármacos , Imunossupressores/farmacologia , Animais , Antígenos CD/imunologia , Venenos de Abelha/administração & dosagem , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Quimiocina CCL21/administração & dosagem , Células Dendríticas/imunologia , Relação Dose-Resposta a Droga , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Imunossupressores/administração & dosagem , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima/efeitos dos fármacosRESUMO
Typical cerebellar or spinal cord hemangioblastoma is often solitary and has a benign clinical course, whereas disseminated hemangioblastomatosis is extremely rare. We report a 75-year-old man with disseminated "leptomeningeal" hemangioblastomatosis and concurrent paraneoplastic limbic encephalitis who died of this disease. The patient presented with gait problems and cognitive deficits, and was diagnosed with a cervical spinal tumor. Surgical resection achieved an apparent gross total resection, but later the patient began experiencing severe cognitive decline. His condition progressively deteriorated during the next few months, and he died 15 months after his initial surgery. Autopsy revealed disseminated extramedullary intradural hemangioblastomatosis with extensive leptomeningeal nodules involving the entire spinal cord, medulla, pons, and midbrain, as well as histologic features of limbic encephalitis. There was no evidence of von Hippel-Lindau disease, and no specific etiology was identified for the dementia. To the best of our knowledge, this is the first case of limbic encephalitis occurring in the setting of disseminated hemangioblastomatosis.