195 research outputs found

    Primary Hyperparathyroidism Patients with Positive Preoperative Sestamibi Scan and Negative Ultrasound Are More Likely to Have Posteriorly Located Upper Gland Adenomas (PLUGs)

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    BackgroundStandard preoperative imaging for primary hyperparathyroidism usually includes sestamibi scanning (MIBI) and ultrasound (US). In a subset of patients with a positive MIBI and a negative US, we hypothesize that the parathyroid adenomas are more likely to be located posteriorly in the neck, where anatomically they are more difficult to detect by US.MethodsWe retrospectively reviewed the records of 661 patients treated for primary hyperparathyroidism between 2004 and 2009 at a tertiary referral center. We included patients who for their first operation had a MIBI that localized a single lesion in the neck and an US that found no parathyroid adenoma. We excluded patients with persistent or recurrent hyperparathyroidism, and patients with MIBIs that were negative, that had more than one positive focus, or that had foci outside of the neck. Sixty-six cases were included in the final analysis.ResultsA total of 54 patients (83%) had a single adenoma, 4 (6%) had double adenomas, and 7 (11%) had hyperplasia. Thirty-three patients (51%) had a single upper gland adenoma; 19 of these (58%) were posteriorly located upper gland adenomas (PLUGs). PLUGs occurred more often on the right side than on the left (P = 0.048, Fisher's test). PLUGs were also larger than other single adenomas (mean 1.85 vs. 1.48 cm, P = 0.021, t-test). Seventy-six percent of patients successfully underwent a unilateral or focused exploration. Six patients (9%) had persistent disease, which is double our group's overall average (4-5%).ConclusionsPrimary hyperparathyroid patients with preoperative positive MIBI and negative US are more likely to have PLUGs

    A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

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    Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

    Inflammatory mediators in breast cancer: Coordinated expression of TNFα & IL-1ÎČ with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition

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    <p>Abstract</p> <p>Background</p> <p>The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1ÎČ were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course.</p> <p>Methods</p> <p>The expression of CCL2, CCL5, TNFα and IL-1ÎČ was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma <it>In Situ </it>(DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments.</p> <p>Results</p> <p>CCL2, CCL5, TNFα and IL-1ÎČ were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1ÎČ in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1ÎČ expression. These results suggest progression-related roles for TNFα and IL-1ÎČ in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1ÎČ compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1ÎČ) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1ÎČ acts jointly with other pro-malignancy factors to promote disease relapse.</p> <p>Conclusions</p> <p>Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1ÎČ may be important for disease course, and that TNFα & IL-1ÎČ may promote disease relapse. Further <it>in vitro </it>and <it>in vivo </it>studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.</p

    An interlaboratory comparison of mid-infrared spectra acquisition: Instruments and procedures matter

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    Diffuse reflectance spectroscopy has been extensively employed to deliver timely and cost-effective predictions of a number of soil properties. However, although several soil spectral laboratories have been established worldwide, the distinct characteristics of instruments and operations still hamper further integration and interoperability across mid-infrared (MIR) soil spectral libraries. In this study, we conducted a large-scale ring trial experiment to understand the lab-to-lab variability of multiple MIR instruments. By developing a systematic evaluation of different mathematical treatments with modeling algorithms, including regular preprocessing and spectral standardization, we quantified and evaluated instruments' dissimilarity and how this impacts internal and shared model performance. We found that all instruments delivered good predictions when calibrated internally using the same instruments' characteristics and standard operating procedures by solely relying on regular spectral preprocessing that accounts for light scattering and multiplicative/additive effects, e.g., using standard normal variate (SNV). When performing model transfer from a large public library (the USDA NSSC-KSSL MIR library) to secondary instruments, good performance was also achieved by regular preprocessing (e.g., SNV) if both instruments shared the same manufacturer. However, significant differences between the KSSL MIR library and contrasting ring trial instruments responses were evident and confirmed by a semi-unsupervised spectral clustering. For heavily contrasting setups, spectral standardization was necessary before transferring prediction models. Non-linear model types like Cubist and memory-based learning delivered more precise estimates because they seemed to be less sensitive to spectral variations than global partial least square regression. In summary, the results from this study can assist new laboratories in building spectroscopy capacity utilizing existing MIR spectral libraries and support the recent global efforts to make soil spectroscopy universally accessible with centralized or shared operating procedures

    A comprehensive overview of radioguided surgery using gamma detection probe technology

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    The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology
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