ORCID Profile
0000-0002-9091-0512
Current Organisations
Baylor College of Medicine
,
King's College Hospital
,
Australian National University
,
Heinrich-Heine-Universitat Düsseldorf
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Publisher: The Endocrine Society
Date: 2000
DOI: 10.1210/JC.85.1.441
Publisher: Springer Science and Business Media LLC
Date: 12-2001
Abstract: The arterial ketone body ratio is calculated as the ratio of arterial levels of acetoacetate/beta-hydroxybutyrate. It correlates with survival in experimental hemorrhagic shock and outcome after liver surgery and myocardial infarction. Procedures for determination of ketone bodies are often laborious and unreliable. As yet the relationship between results from arterial and venous s les is unclear. We therefore describe the determination of the ketone bodies acetoacetate and 3-hydroxybutyrate by an easy, reliable, rapid, inexpensive enzymatic assay using 3-hydroxybutyrate dehydrogenase (E.C. 1.1.1.30) in a semi-automated setting that does not require deproteinization. Preanalytical parameters, including separation from corpuscular elements within 1 h and storage on ice for less than 1 h, must be strictly observed to avoid rapid decay of acetoacetate by spontaneous decarboxylation. The assay has high sensitivity, specificity (+/-5%), and precision (CV <2.5%) with a measurable range of 5-500 micromol/l for either ketone body, and requires only 23.5 microl of plasma. At temperatures below -17 degrees C plasma may be stored for prolonged periods. Results from prospectively scheduled simultaneous s ling of arterial blood and venous blood from the right atrium in 100 consecutive patients with severe multiple trauma (mean Injury Severity Score 38+/-13) support the view that the lung has no role in ketone body metabolism. We conclude that central venous blood can safely be substituted for arterial blood for determination of the ketone body ratio.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 05-2017
Publisher: Elsevier BV
Date: 07-2014
Publisher: Public Library of Science (PLoS)
Date: 19-04-2021
DOI: 10.1371/JOURNAL.PPAT.1009522
Abstract: Although HIV infection inhibits interferon responses in its target cells in vitro , interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, pDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.
Publisher: Public Library of Science (PLoS)
Date: 13-10-2016
Publisher: Bioscientifica
Date: 04-2023
DOI: 10.1530/ERC-22-0287
Abstract: Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle–Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a ‘centre of excellence’ with a track record in PC management.
Publisher: Wiley
Date: 06-06-2012
DOI: 10.1111/J.1365-2265.2012.04336.X
Abstract: Papillary thyroid cancer (PTC) is a common endocrine cancer and frequently presents with lymph node (LN) metastases. The frequency of LN metastases in the lateral compartment and their surgical removal are poorly defined. There are no prospective randomised controlled trials addressing an eventual outcome difference relating to the extent of the initial surgical approach. The aim of this study was to define the extent of lateral LN involvement and the role of imaging in identification of these metastatic LN. A systematic review of studies of patients with PTC undergoing either prophylactic or therapeutic lymphadenectomy of the lateral cervical compartment. Studies involving imaging modalities in the detection of lateral cervical LNs in PTC were also analysed. Systematic review on the frequency of lateral LN metastases and their detection using various imaging tools identified 19 studies containing data on 5587 patients undergoing prophylactic or imaging-guided removal of the lateral compartment. Imaging-guided surgery retrieved cancerous lateral LNs in 446/3178 or 14% of eligible patients, whilst prophylactic lateral neck dissection yielded histopathological proof of cancer in 1177/204 or 57·5% of patients. The frequency of lateral compartment metastases increased with T stage. The sensitivity of ultrasound and CT was poor as low as 27% when accurately calculated. Metastatic cervical LNs were found in more than half of patients when prophylactic lateral LN dissection was performed. Use of conventional imaging for the selection of the surgical approach to the lateral cervical compartment may commonly identify stage N1a instead of N1b and thus lead to false stage assignment as stage III rather than stage IV, concealing the severe prognostic implications of this stage progression in in idual patients.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 11-2020
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
DOI: 10.1016/J.IJSU.2009.06.005
Abstract: Polyarteritis nodosa (PAN) of the breast is a rare condition where literature review identified eleven patients so far. The clinical presentation ranged from localized disease involving the breast parenchyma and skin only to breast manifestations as part of systemic PAN. The diagnosis of PAN could be challenging as it can mimic breast cancer, inflammatory carcinomatosis or breast infection including mastitis and necrotizing fasciitis. The key importance is accurate diagnosis to avoid unnecessary other treatment modalities and the timely recognition of PAN in cases of localized forms. The authors present three new cases which represent the full range of the clinical spectrum and their management.
Publisher: Elsevier BV
Date: 11-2017
Publisher: MDPI AG
Date: 24-09-2019
DOI: 10.3390/EN12193630
Abstract: Accurate prediction of pollutant dispersion is vital to the energy industry. This study investigated the Computational Fluid Dynamics (CFD) simulation of pollutant emission in a natural draft dry cooling tower (NDDCT) with flue gas injection. In order to predict the diffusion and distribution characteristics of the pollutant more accurately, Large Eddy Simulation (LES) was applied to predict the flow field and pollutant concentration field and compared with Reynolds Average Navier-Stokes (RANS) and Unsteady Reynolds Average Navier-Stokes (URANS). The relationship between pollutant concentration pulsation and velocity pulsation is emphatically analyzed. The results show that the flow field and concentration field simulated by RANS and URANS are very close, and the maximum value of LES is about 43 times that of RANS and URANS for the prediction of pollutant concentration in the inner shell of cooling tower. Pollutant concentration is closely related to local flow field velocity. RANS and URANS differ greatly from LES in flow field prediction, especially at the outlet and downwind of cooling tower. Compared with URANS, LES can simulate flow field pulsation with a smaller scale and higher frequency.
Publisher: Springer Berlin Heidelberg
Date: 2007
Publisher: BMJ
Date: 03-05-2011
Publisher: Springer Science and Business Media LLC
Date: 14-12-1999
Publisher: Georg Thieme Verlag KG
Date: 15-07-2009
Abstract: Oncogene lification is frequent in many epithelial tumors and often associated with advanced tumor progression. In different epithelial neoplasias it helps to provide prognostic information on in idual patients. The present study was performed to evaluate the hitherto unknown prevalence of INT-2 gene lification and its potential usefulness as prognostic marker in patients with human thyroid cancer. We used differential quantitative polymerase chain reaction and fluorescent DNA technique as a reliable method to detect low copy-number lification of oncogenes from archival carcinoma specimens. Sequences from the int-2 gene and the single copy gamma-interferon gene were lified simultaneously by PCR and quantified on a fluorescence activated sequencer. Native tumor tissue from 63 patients with differentiated thyroid cancer (43 papillary, 3 oncocytary, and 17 follicular) and from 12 goiters was analyzed by differential quantitative polymerase chain reaction. The study group contained many far advanced tumors. 40% of tumors were recurrent, 35% were staged T4 tumors and 70% presented with lymph node metastases. The prevalence of INT-2 lification was 12% for follicular and 7% for papillary carcinomas. In goiter tissue no lification was found. Amplification was only 2-4fold in positive cases. Low grade lification is of no apparent importance in differentiated thyroid cancer.
Publisher: Springer Science and Business Media LLC
Date: 10-03-2010
DOI: 10.1245/S10434-010-1003-6
Abstract: Parathyroid cancer is rare and often fatal. This review provides an in-depth analysis of 330 clinical cases reported in detail. These data are used to inform a proposal for a hitherto lacking TNM staging system. All case reports or series with sufficient case details of parathyroid cancer were identified from PubMed, and data were analyzed using SPSS. Of 330 patients, 117 (35%) died of disease and 207 (63%) experienced recurrence in a total of 2007 follow-up years and a mean length of follow-up of 6.1 years. Histopathology findings rather than biochemical or clinical features predict outcome. In univariate analysis, survival and recurrence rates are significantly influenced by gender (male relative risk [RR] 1.7, 95% confidence interval [95% CI] 1.0-2.7, P < .01), and presence of vascular invasion (RR 4.3, 95% CI 1.1-17.7, P < .01), or lymph node metastases (RR 6.2, 95 %CI 0.9-42.9, P < .001). Failure to perform oncological surgery carries a high risk for recurrence and death (local versus en bloc resection RR 2.0, CI 1.2-3.2, P < .01) as for redo surgery. Staging by a novel anatomy-based TNM system identifies significant outcome variation as to recurrence and death. Separation of patients into low and high risk identifies a 3.5-7.0 fold higher risk of recurrence and death (P < .01) for the high-risk group. Distant metastases predominantly target mediastinum and lung. Understaging and undertreatment are shown to contribute to high recurrence rates and death toll. To improve outcome, en bloc resection including central lymph node dissection should be the minimal surgical approach in any patient with suspected parathyroid cancer.
Publisher: BMJ
Date: 20-05-2014
Publisher: Wiley
Date: 07-12-2020
DOI: 10.1002/TPG2.20066
Abstract: Stripe or yellow rust, caused by Puccinia striiformis Westend. f. sp. tritici is a major threat to bread wheat production worldwide. The breakdown in resistance of certain major genes and newly emerging aggressive races of stripe rusts pose serious concerns in all main wheat growing areas of the world. To identify new sources of resistance and associated QTL for effective utilization in future breeding programs an association mapping (AM) panel comprising of 600 bread wheat landraces collected from eight different countries conserved at ICARDA gene bank were evaluated for seedling and adult plant resistance against the PstS2 and Warrior races of stripe rust at the Regional Cereal Rust Research Center (RCRRC), Izmir, Turkey during 2016, 2018 and 2019. A set of 25,169 informative SNP markers covering the whole genome were used to examine the population structure, linkage disequilibrium and marker‐trait associations in the AM panel. The genome‐wide association study (GWAS) was carried out using a Mixed Linear Model (MLM). We identified 47 SNP markers across 19 chromosomes with significant SNP‐trait associations for both seedling stage and adult plant resistance. The threshold of significance for all SNP‐trait associations was determined by the false discovery rate (q) ≤ 0.05. Three genomic regions ( QYr.1D_APR, QYr.3A_seedling and QYr.7D_seedling ) identified in this study do not correspond to previously reported Yr genes or QTL, suggesting new genomic regions for stripe rust resistance.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2001
Publisher: Elsevier BV
Date: 05-2021
Publisher: Massachusetts Medical Society
Date: 20-08-2009
Publisher: Springer Science and Business Media LLC
Date: 10-05-2011
DOI: 10.1007/S00330-011-2141-3
Abstract: Nearly all reported parathyroid cancers are >15 mm at presentation. The objective was to identify ultrasound criteria of malignancy in parathyroid lesions of >15 mm in size. This study was approved by a local ethics committee. A retrospective review of patients identified from a database from 2004-2009 was performed. All patients underwent ultrasound imaging according to the protocol. Two trained observers categorized findings using the pre-determined features: shape, calcification, pattern of vascularity, local infiltration and internal lesion gray scale appearances. Sixty-nine patients (mean age 54.3 years, range 19-79 years male = 16, female = 53) fulfilled the criteria of a parathyroid lesion >15 mm 8/69 (11.6%) with parathyroid cancer and 61/69 (88.4%) with benign solitary parathyroid adenoma. A high positive predictive value (PPV) for cancer was identified for infiltration (PPV 100%) and calcification (PPV 100%), whilst a high negative predictive value (NPV) was found for the absence of suspicious vascularity (NPV 97.6%), a thick capsule (NPV 96.7) and inhomogeneity (NPV 100%). In lesions >15 mm systematic ultrasound assessment of specific features provides a valuable tool to identify parathyroid cancers before surgery.
Publisher: MDPI AG
Date: 24-12-2020
DOI: 10.3390/RS13010038
Abstract: In Antarctica, spectral mapping of altered minerals is very challenging due to the remoteness and inaccessibility of poorly exposed outcrops. This investigation evaluates the capability of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite remote sensing imagery for mapping and discrimination of phyllosilicate mineral groups in the Antarctic environment of northern Victoria Land. The Mixture-Tuned Matched-Filtering (MTMF) and Constrained Energy Minimization (CEM) algorithms were used to detect the sub-pixel abundance of Al-rich, Fe3+-rich, Fe2+-rich and Mg-rich phyllosilicates using the visible and near-infrared (VNIR), short-wave infrared (SWIR) and thermal-infrared (TIR) bands of ASTER. Results indicate that Al-rich phyllosilicates are strongly detected in the exposed outcrops of the Granite Harbour granitoids, Wilson Metamorphic Complex and the Beacon Supergroup. The presence of the smectite mineral group derived from the Jurassic basaltic rocks (Ferrar Dolerite and Kirkpatrick Basalts) by weathering and decomposition processes implicates Fe3+-rich and Fe2+-rich phyllosilicates. Biotite (Fe2+-rich phyllosilicate) is detected associated with the Granite Harbour granitoids, Wilson Metamorphic Complex and Melbourne Volcanics. Mg-rich phyllosilicates are mostly mapped in the scree, glacial drift, moraine and crevasse fields derived from weathering and decomposition of the Kirkpatrick Basalt and Ferrar Dolerite. Chlorite (Mg-rich phyllosilicate) was generally mapped in the exposures of Granite Harbour granodiorite and granite and partially identified in the Ferrar Dolerite, the Kirkpatrick Basalt, the Priestley Formation and Priestley Schist and the scree, glacial drift and moraine. Statistical results indicate that Al-rich phyllosilicates class pixels are strongly discriminated, while the pixels attributed to Fe3+-rich class, Fe2+-rich and Mg-rich phyllosilicates classes contain some spectral mixing due to their subtle spectral differences in the VNIR+SWIR bands of ASTER. Results derived from TIR bands of ASTER show that a high level of confusion is associated with mafic phyllosilicates pixels (Fe3+-rich, Fe2+-rich and Mg-rich classes), whereas felsic phyllosilicates (Al-rich class) pixels are well mapped. Ground truth with detailed geological data, petrographic study and X-ray diffraction (XRD) analysis verified the remote sensing results. Consequently, ASTER image-map of phyllosilicate minerals is generated for the Mesa Range, C bell and Priestley Glaciers, northern Victoria Land of Antarctica.
Publisher: AME Publishing Company
Date: 06-2019
Publisher: Elsevier BV
Date: 10-2020
Publisher: The Endocrine Society
Date: 02-2004
Abstract: Mounting evidence exists for a role of the CRH system in energy balance, including a direct influence on human adipocytes, the regulation of adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity, and cortisol formation. We characterized the expression of CRH receptors 1 and 2 and CRH-like peptides stresscopin and urocortin in human adipose tissue in comparison with other peripheral tissues, adrenal, and heart. The effect of CRH on CRH receptor and CRH-like peptide expression was analyzed in isolated human adipocytes using quantitative TaqMan PCR. CRH receptors were detectable in fat tissue at mRNA and protein levels. CRH-R2 expression in fat was comparable with its expression in the heart, the organ with the highest CRH-R2 expression known. CRH-R1:CRH-R2 ratio varied according to fat-depot type whereas CRH-R1 expression was higher in sc fat than in visceral fat, the opposite was true for CRH-R2. Adipose tissue also expressed urocortin and stresscopin, the predominant ligands of peripheral CRH-R2. CRH down-regulated CRH-R1 and CRH-R2 mRNA expression in isolated adipocytes. These data, together with the recently published observation that CRH regulates adipocyte metabolism by down-regulating 11 beta-hydroxysteroid dehydrogenase, indicate that a CRH system exists within human adipose tissue. This system could be implicated in energy homeostasis and in mediating the anorexic effects of CRH at adipose level.
Publisher: Georg Thieme Verlag KG
Date: 02-2000
Abstract: The discovery of mutations of the menin gene in a few multiple endocrine neoplasma type 1 (MEN I)-associated lipomas and loss of heterozygosity (LOH) on chromosome 11q13 in some sporadic lipomas has stimulated the hypothesis that lipomas may belong to the group of sporadic tumors caused by defects of the gene responsible for MEN I. Since it is unclear if the above hypothesis applies to all patients with lipoma or just to specific subsets, we searched to enlarge the database on this topic. For this purpose, we identified two patients with multiple cutaneous lipomas. One had an additional pituitary adenoma and familial presentation of multiple lipomas, the other had recurrent goiter in the setting of a family history of adenomatous goiter. Deoxyribonucleic acid (DNA) was analyzed by complete direct DNA sequencing of all coding exons and splice junctions of the MEN I gene. No mutation was identified in the coding exons of the menin gene. In contrast to former data on sporadic lipomas, these data are the first to render evidence that mutations of the MEN I gene may not be responsible for the formation of multiple lipomas, even if they appear in the context of other endocrine tumors.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Springer Science and Business Media LLC
Date: 21-06-2019
DOI: 10.1038/S41467-019-10697-W
Abstract: Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c + dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c + DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33 low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2004
DOI: 10.1097/00024382-200404000-00003
Abstract: A dysbalanced immune response is thought to account for a substantial part of the morbidity and mortality after severe trauma. The cytokine interleukin-10 (IL-10) suppresses the transcription of proinflammatory cytokines, mainly in macrophages and monocytes. The objectives of this prospective study in a level I trauma center in Germany were to examine the distribution of IL-10 promoter polymorphisms in a cohort of severely injured patients, to measure IL-10 cytokine levels and relate these to the genotype, and to identify associations of IL-10 polymorphisms with the incidence of severe multiple organ dysfunction syndrome (MODS). The genotypes of polymorphisms -592 and -1082 were determined by polymerase chain reaction (PCR) and restriction cleavage with Rsa 1 or Mnl I, respectively. We analyzed 119 severely injured trauma patients [mean Injury Severity Score (ISS) 38.0 +/- 13.2]. The frequency of the -1082A allele was 0.542, and that of the -592C allele was 0.807. IL-10 polymorphisms were not significantly associated with mean systemic IL-10 cytokine levels 6, 12, and 18 h after admission to the ICU. Carriers of the genotype -592AC had significantly higher overall MOD scores than non-AC carriers (P = 0.018 P(corr) = 0.036). The genotypes of the IL-10 SNP -1082 were not significantly associated with MOD scores. A multivariate Cox hazard regression analysis including important factors of the patients' anatomic and physiological trauma impact revealed only the shock index, the severity of the head injury, and the IL-10 -592 genotype AC as significant independent risk factors for the development of MODS. In this multivariate analysis, carriers of the genotype -592AC displayed a 3.3-fold increase in the relative risk of developing a MODS (P = 0.008, hazard ratio 3.29, 95% CI 1.36-7.97). Our data suggest a possible link between the AC genotype of the -592 single nucleotide polymorphism and significantly higher mean MOD scores. The AC genotype was associated in multivariate analysis with a higher relative risk of MODS in multiply injured patients. Further investigations in larger cohorts need to focus on the potential diagnostic and therapeutic options of this SNP.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2014
DOI: 10.1245/S10434-014-3530-Z
Abstract: Parathyroid cancer has a poor mid-term prognosis, often because of local recurrence, observed in half of all patients. Modern diagnostic workup increasingly enables a preoperative diagnosis of parathyroid cancer. There is limited evidence that more comprehensive oncologic surgery can reduce the risk of local recurrence. This study aims to identify the best specific surgical approach in parathyroid cancer. This observational cohort study comprises 19 consecutive patients who had undergone oncologic or nononcologic resection for parathyroid cancer. Baseline parameters were compared by using univariate analysis outcomes were assessed by χ (2) testing and Kaplan-Meier statistics. Fifteen of 19 patients were primarily operated on in our tertiary center between 1996 and 2013, and four were referred for follow-up because of their cancer diagnosis. Patient cohorts defined by histologic R-status were comparable for established risk factors: sex, calcium levels, low-risk/high-risk status, and presence of vascular invasion. Oncologic resections were performed in 13 of 15 patients primarily treated in the center and 0 of 4 treated elsewhere (χ (2) = 5.6 p < 0.01). R0 margins were achieved in 11 of 13 (85 %) undergoing oncologic resection and 1 of 6 (17 %) undergoing local excision (χ (2) = 8.1 p < 0.01). R0 margins and primary oncologic resection were associated with higher disease-free survival rates (χ (2) = 7.9 p = 0.005 and χ (2) = 4.7 p = 0.03, respectively). Revision surgery achieved R0 margins in only 2 of 4 (50 %) of patients. In parathyroid cancer, a more comprehensive surgery (primary oncologic resection) provides significantly better outcomes than local excision as a result of reduction of R1 margins and locoregional recurrence.
Publisher: Springer Science and Business Media LLC
Date: 24-12-2014
DOI: 10.1038/TPJ.2013.42
Abstract: Bariatric surgery is a well-established approach to improve metabolic disease in morbidly obese patients with high cardiovascular risk. The post-operative normalization of lipid metabolism has a central role in the prevention of future cardiovascular events. The aim of the present study therefore was to characterize changes of plasma lipidomic patterns, consisting of 229 lipid species of 13 lipid classes, 3 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients with and without diabetes. RYGB resulted in a 15-32% decrease of body mass index, which was associated with a significant reduction of total cholesterol (TC, -28.3% P=0.02), LDL-cholesterol (LDL-C, -26.8% P=0.03) and triglycerides (TGs, -63.0% P=0.05) measured by routine clinical chemistry. HDL-cholesterol remained unchanged. The effect of RYGB on the plasma lipidomic profile was characterized by significant decreases of 87 lipid species from triacylglycerides (TAGs), cholesterol esters (CholEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), phosphatidylethanolamine ethers (PEOs), phosphatidylinositols (PIs) and ceramides (Cers). The total of plasma lipid components exhibited a substantial decline of 32.6% and 66 lipid species showed a decrease by over 50%. A direct correlation with HbA1C values could be demonstrated for 24 in idual lipid species (10 TAG, three CholE, two LPC, one lysophosphatidylcholine ethers (LPCO) (LPC ether), one PC, two phosphatidylcholine ethers (PCO) and five Cer). Notably, two lipid species (TAG 58:5 and PEO 40:5) were inversely correlated with HbA1C. LPCO, as single whole lipid class, was directly related to HbA1C. These data indicate that RYGB-induced modulation of lipidomic profiles provides important information about post-operative metabolic adaptations and might substantially contribute to improvements of glycemic control. These striking changes in the human plasma lipidome may explain acute, weight independent and long-term effects of RYGB on the cardiovascular system, mental status and immune regulation.
Publisher: MDPI AG
Date: 16-04-2020
DOI: 10.3390/RS12081261
Abstract: There are a significant number of image processing methods that have been developed during the past decades for detecting anomalous areas, such as hydrothermal alteration zones, using satellite images. Among these methods, dimensionality reduction or transformation techniques are known to be a robust type of methods, which are helpful, as they reduce the extent of a study area at the initial stage of mineral exploration. Principal component analysis (PCA), independent component analysis (ICA), and minimum noise fraction (MNF) are the dimensionality reduction techniques known as multivariate statistical methods that convert a set of observed and correlated input variables into uncorrelated or independent components. In this study, these techniques were comprehensively compared and integrated, to show how they could be jointly applied in remote sensing data analysis for mapping hydrothermal alteration zones associated with epithermal Cu–Au deposits in the Toroud-Chahshirin range, Central Iran. These techniques were applied on specific subsets of the advanced spaceborne thermal emission and reflection radiometer (ASTER) spectral bands for mapping gossans and hydrothermal alteration zones, such as argillic, propylitic, and phyllic zones. The fuzzy logic model was used for integrating the most rational thematic layers derived from the transformation techniques, which led to an efficient remote sensing evidential layer for mineral prospectivity mapping. The results showed that ICA was a more robust technique for generating hydrothermal alteration thematic layers, compared to the other dimensionality reduction techniques. The capabilities of this technique in separating source signals from noise led to improved enhancement of geological features, such as specific alteration zones. In this investigation, several previously unmapped prospective zones were detected using the integrated hydrothermal alteration map and most of the known hydrothermal mineral occurrences showed a high prospectivity value. Fieldwork and laboratory analysis were conducted to validate the results and to verify new prospective zones in the study area, which indicated a good consistency with the remote sensing output. This study demonstrated that the integration of remote sensing-based alteration thematic layers derived from the transformation techniques is a reliable and low-cost approach for mineral prospectivity mapping in metallogenic provinces, at the reconnaissance stage of mineral exploration.
Publisher: MDPI AG
Date: 28-11-2022
Abstract: Parathyroid cancer (PC) is rare, but its pre-operative recognition is important to choose appropriate access strategies and achieve oncological clearance. This study characterizes features of mediastinal parathyroid cancer (MPC) and explores criteria aiding in the pre-operative recognition of malignancy. We assembled data from 502 patients with mediastinal parathyroid neoplasms (MPNs) from a systematic review of the literature 1968–2020 (n = 467) and our own patient cohort (n = 35). Thirty-two of the 502 MPNs (6.4%) exhibited malignancy. Only 23% of MPC patients underwent oncological surgery. Local persistence and early recurrence at a median delay of 24 months were frequent (45.8%), and associated with a 21.7-fold (95%CI 1.3–351.4 p = 0.03) higher risk of death due to disease. MPCs (n = 30) were significantly larger than cervical PC (n = 330), at 54 ± 36 mm vs. 35 ± 18 mm (χ2 = 20 p 0.0001), and larger than mediastinal parathyroid adenomas (MPA n = 226) at 22 ± 15 mm (χ2 = 33 p 0.01). MPC occurred more commonly in males (60% p 0.01), with higher calcium (p 0.01) and parathyroid hormone (PTH) levels (p 0.01) than MPA. Mediastinal lesions larger than 3.0 cm and associated with a corrected calcium ≥ 3.0 mM are associated with a more than 100-fold higher odds ratio of being malignant (OR 109.2 95%CI 1.1–346 p 0.05). The composite 3 + 3 criterion recognized 74% of all MPC with an accuracy of 83%. Inversely, no MPN presenting with a calcium 3.0 mM and size 3.0 cm was malignant. When faced with pHPT in mediastinal location, consideration of the 3 + 3 rule may trigger an oncological team approach based on simple, available criteria.
Publisher: Frontiers Media SA
Date: 1992
Publisher: Life Science Alliance, LLC
Date: 21-03-2023
Abstract: Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I 2 ), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I 2 . Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.
Publisher: The Endocrine Society
Date: 07-2002
Abstract: Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the entire genome of a tumor to be surveyed for gains and losses of DNA copy sequences. A limited number of studies reporting the use of this technique in adult adrenocortical tumors have yielded conflicting results. In this study we performed CGH analysis on 13 malignant, 18 benign, and 1 tumor of indeterminate malignant potential with the aim of identifying genetic loci consistently implicated in the development and progression of adrenocortical tumors. Tissue s les from 32 patients with histologically proven adrenocortical tumors were available for CGH analysis. CGH changes were seen in all cancers, 11 of 18 (61%) adenomas, and the 1 tumor of indeterminate malignant potential. Of the adrenal cancers, the most common gains were seen on chromosomes 5 (46%), 12 (38%), 19 (31%), and 4 (31%). Losses were most frequently seen at 1p (62%), 17p (54%), 22 (38%), 2q (31%), and 11q (31%). Of the benign adenomas, the most common change was gain of 4q (22%). Mann-Whitney analysis showed a highly significant difference between the cancer group (mean changes, 7.6) and the adenoma group (mean changes, 1.1) for the number of observed CGH changes (P & 0.01). Logistic regression analysis showed that the number of CGH changes was highly predictive of tumor type (P & 0.01). This study has identified several chromosomal loci implicated in adrenocortical tumorigenesis. Activation of a protooncogene(s) on chromosome 4 may be an early event, with progression from adenoma to carcinoma involving activation of oncogenes on chromosomes 5 and 12 and inactivation of tumor suppressor genes on chromosome arms 1p and 17p.
Publisher: Georg Thieme Verlag KG
Date: 02-2001
DOI: 10.1055/S-2001-11144
Publisher: Bioscientifica
Date: 03-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2003
DOI: 10.1097/00003246-200301000-00011
Abstract: To examine the influence of genetic variations in heat shock proteins on trauma outcome. Prospective, noninterventional, single-center study. Level I trauma center. Eighty consecutive severe multiple trauma patients. None. Plasma concentrations of interleukin-6 and tumor necrosis factor-alpha were measured over a 5-day course by chemiluminescence-immunoassay. The genotypes of the polymorphisms HSPA1B (HSP70-2) G1538A and HSPA1L (HSP70-Hom) C2437T were determined by polymerase chain reaction and restriction cleavage with PstlI or NcoI, respectively. Allele frequency of the HSPA1B 1538 G allele was 0.569, and that of the HSPA1L 2437 T allele was 0.821. Interleukin-6 concentrations rapidly increased and dropped to almost normal after 5 days, whereas tumor necrosis factor-alpha concentrations increased until day 5. Patients carrying the genotypes HSPA1B AG or HSPA1L CT had significantly higher plasma concentrations of tumor necrosis factor-alpha and interleukin-6 compared with those with genotype GG or TT. Presence of the HSPA1L genotype CT also was a significant risk factor to develop liver failure (odds ratio, 4.6 95% confidence interval, 1.5-14.1) and to acquire at least one complication severe enough to score three points according to the Denver multiple organ failure score (odds ratio, 3.0 95% confidence interval, 1.1-9.2). The data indicate that genetic variations of the heat shock proteins HSPA1B and HSPA1L may contribute to clinical outcome after severe injury.
Publisher: Springer Science and Business Media LLC
Date: 10-06-1998
Abstract: BRAF is frequently mutated in human cancer and the RASopathy syndromes, with RASopathy mutations often observed in the cysteine-rich domain (CRD). Although the CRD participates in phosphatidylserine (PS) binding, the RAS-RAF interaction, and RAF autoinhibition, the impact of these activities on RAF function in normal and disease states is not well characterized. Here, we analyze a panel of CRD mutations and show that they increase BRAF activity by relieving autoinhibition and/or enhancing PS binding, with relief of autoinhibition being the major factor determining mutation severity. Further, we show that CRD-mediated autoinhibition prevents the constitutive plasma membrane localization of BRAF that causes increased RAS-dependent and RAS-independent function. Comparison of the BRAF- and CRAF-CRDs also indicates that the BRAF-CRD is a stronger mediator of autoinhibition and PS binding, and given the increased catalytic activity of BRAF, our studies reveal a more critical role for CRD-mediated autoinhibition in BRAF regulation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
Publisher: Springer Science and Business Media LLC
Date: 07-2004
DOI: 10.1007/S00104-003-0811-7
Abstract: Decreasing the length of stay is a possible means of cost control in the medical system. Therefore we performed a study to test the feasibility of reducing hospital stay to 2 days after thyroid operation. In a controlled prospective trial, 238 patients were randomly assigned to group A (2 days of stay) or group B (more than 2 days). Studied were medical standard, practicability, patient acceptance, and quality of life. Of those in group A, 56.6% did not leave the hospital at the scheduled 2nd day post operation. Reasons were preoperative hyperthyroidism ( P<0.011), postoperative hypocalcemia ( P<0.03), or unspecific disturbances. In group B, 28% of the patients left before the established borderline of 3-4 days, and only 35% left on the 2nd postoperative day. Reduced length of stay has no negative influence on medical standards. The quality of life of patients leaving the hospital on the 2nd postoperative day was significantly higher. Reducing hospital stay after thyroid operation to 2 postoperative days is desirable and possible without a loss in quality of care, except in case of postoperative complications or unspecific complaints.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Bioscientifica
Date: 07-2012
DOI: 10.1530/EC-12-0028
Abstract: Mitotane (o,p'-DDD), an oral adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC), is reported to inhibit cortisol biosynthesis in vitro and enhance production from exogenous cortisol of urinary 6β-hydroxycortisol and unidentified polar unconjugated metabolites. We examined urinary steroid profiles by gas chromatography–mass spectrometry of patients with histologically confirmed ACC following surgery, receiving a) hydrocortisone alone (three males and three females) and b) mitotane and hydrocortisone (six males and 11 females). S les were collected after plasma mitotane had reached the therapeutic range of 14–20 mg/l. Increased excretion of polar unconjugated steroids during mitotane treatment was confirmed, with 6β-hydroxycortisol and 6β-hydroxy-20-dihydrocortisols predominating. The proportion of additionally hydroxylated metabolites was % in untreated controls and 52, 35–52% (mean, range) in the mitotane plus hydrocortisone group. Ratios of 5α-/5β- and 20β-/20α-metabolites of administered cortisol were decreased 50-, 15-fold, and 14-, 8-fold respectively (males, females – mean values) but with no change in metabolite ratios that reflect oxidoreduction at C11 or C20. Patterns of decrease in 5α- relative to 5β-reduced metabolites were similar to those of patients with 5α-reductase 2 deficiency or on treatment with the 5α-reductase 2 inhibitor finasteride but different from those of patients on dutasteride, indicating specific inhibition of 5α-reductase 2. We conclude that mitotane causes consistent changes in cortisol catabolism, most of which have not been previously recognised. These need not interfere with early detection of ACC recurrence. Induction of 6β-hydroxylation offers an explanation for a reported decrease in cortisol bioavailability. Mitotane also has potential as a unique steroid metabolic probe for 20β-reduction.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2022
DOI: 10.1038/S41526-022-00219-2
Abstract: Astronauts in a microgravity environment will experience significant changes in their cardiopulmonary system. Up until now, there has always been the reassurance that they have real-time contact with experts on Earth. Mars crew however will have gaps in their communication of 20 min or more. In silico experiments are therefore needed to assess fitness to fly for those on future space flights to Mars. In this study, we present an open-source controlled lumped mathematical model of the cardiopulmonary system that is able simulate the short-term adaptations of key hemodynamic parameters to an active stand test after being exposed to microgravity. The presented model is capable of adequately simulating key cardiovascular hemodynamic changes—over a short time frame—during a stand test after prolonged spaceflight under different gravitational conditions and fluid loading conditions. This model can form the basis for further exploration of the ability of the human cardiovascular system to withstand long-duration space flight and life on Mars.
Publisher: Wiley
Date: 17-10-2013
DOI: 10.1111/CEN.12324
Abstract: Phaeochromocytoma [corrected] crisis is an endocrine emergency associated with significant mortality. There is little published guidance on the management of phaeochromocytoma [corrected] crisis. This clinical practice update summarizes the relevant published literature, including a detailed review of cases published in the past 5 years, and a proposed classification system. We review the recommended management of phaeochromocytoma [corrected] crisis including the use of alpha-blockade, which is strongly associated with survival of a crisis. Mechanical circulatory supportive therapy (including intra-aortic balloon pump or extra-corporeal membrane oxygenation) is strongly recommended for patients with sustained hypotension. Surgical intervention should be deferred until medical stabilization is achieved.
Publisher: Elsevier BV
Date: 08-2011
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.EJSO.2005.01.013
Abstract: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue s les were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain lification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.
Publisher: Public Library of Science (PLoS)
Date: 30-12-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2012
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 2001
DOI: 10.1016/S0272-6386(01)80068-8
Abstract: We describe a 36-year-old man who presented with hypocomplementemic urticarial vasculitis syndrome (HUVS) with severe renal involvement. Despite steroid therapy, the patient developed end-stage renal disease (ESRD) leading to chronic hemodialysis therapy. Renal transplantation was performed after hemodialysis therapy (secondary), and the patient developed a typical HUVS relapse 9 months after transplantation despite conventional immunosuppressive therapy that was successfully treated with plasma exchange. This case shows for the first time that HUVS can induce severe renal involvement responsible for ESRD and that HUVS can relapse after renal transplantation. It also suggests that plasma exchange therapy may be of value for rapidly controlling the clinical symptoms.
Publisher: Wiley
Date: 24-03-2004
DOI: 10.1002/IJC.20210
Abstract: Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.
Publisher: MDPI AG
Date: 29-12-2022
Abstract: Long-term outcomes of parathyroid cancer remain poorly documented and unsatisfactory. This cohort includes 25 consecutive parathyroid cancer patients with median follow-up of 10.7 years (range 4.1–26.5 years). Pre-operative work-up in the center identified a suspicion of parathyroid cancer in 17 patients. En bloc resection, including the recurrent laryngeal nerve in 4/17 (23.5%), achieved cancer-free resection margins (R0) in 82.4% and lasting loco-regional disease control in 94.1%. Including patients referred after initial surgery elsewhere, R0 resection was achieved in merely 17/25 (68.0%) of patients. Cancer-positive margins (R1) in 8 patients led to local recurrence in 50%. On multivariate analysis, only margin status prevailed as independent predictor of recurrence free survival (χ2 19.5, p 0.001). Local excision alone carried a 3.5-fold higher risk of positive margins than en bloc resection (CI95: 1.1–11.3 p = 0.03), and a 6.4-fold higher risk of locoregional recurrence (CI95: 0.8–52.1 p = 0.08). R1-status was associated with an 18.0-fold higher risk of recurrence and redo surgery (CI95: 1.1–299.0 p = 0.04), and a 22.0-fold higher probability of radiation (CI95: 1.4–355.5 p = 0.03). In patients at risk, adjuvant radiation reduced the actuarial risk of locoregional recurrence (p = 0.05). When pre-operative scrutiny resulted in upfront oncological surgery achieving cancer free margins, it afforded 100% recurrence free survival at 5- and 10-year follow-up, whilst failure to achieve clear margins caused significant burden by outpatient admissions (176 vs. 4 days χ2 980, p 0.001) and exposure to causes for concern (1369 vs. 0 days χ2 11.3, p = 0.003). Although limited by cohort size, our study emphasizes the paradigm of getting it right the first time as key to improve survivorship in a cancer with excellent long-term prognosis.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2012
Abstract: Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any in idual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.
Publisher: Oxford University Press (OUP)
Date: 06-2004
Abstract: Pancreas isum is the most common congenital anomaly of the pancreas, characterized by missing fusion of the ventral and dorsal pancreatic duct. It may cause pancreatitis, but is rarely associated with malignancy.We report herein for the first time the rare association, in a symptomless patient, of multiple neuroendocrine tumors of the pancreas with pancreas isum and a failure of the exocrine system. Diagnosis was made incidentally by routine abdominal ultrasound. Laboratory examinations and a fine-needle aspiration revealed the neuroendocrine nature of the tumor. Spleen-preserving left pancreas resection was performed, with evidence of multiple neuroendocrine tumors of the pancreas with the typical histological characteristics. Eighteen months later the patient is still free of tumor burden.
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/CEN.12458
Abstract: Adrenocortical neoplasms are classically ided into adenomas (ACA) and carcinomas (ACC). Heterogeneous appearance and greater size are criteria to suggest malignancy, along with the urinary steroid profile (USP). The presence of regression and myelolipomatous changes in adenomas (ACA-RML) can contribute to confusion with ACC and its USP remains unknown. To evaluate the features of ACA-RML in comparison with other adrenocortical neoplasms. We selected consecutive ACA (11), ACA-RML (7) and ACC (13) cases for which USP analysis was performed before surgery and tissue was available for histological evaluation (King's College Hospital, 2005-2012). Cases were classified according to WHO and Armed Forces Institute of Pathology criteria. USPs were obtained by gas chromatography/mass spectrometry. Total excretion of in idual steroids and indices (sums and ratios chosen to reflect steroid metabolic activity) were compared between ACA-RML, ACA and ACC. In comparison with ACA, tumours in ACA-RML were significantly larger (8·5 ± 2·4 vs 3·5 ± 1·0, P = 0·002), presented in older patients and showed relatively higher incidence in males. Mitotic figure counts were significantly lower (0·39 ± 0·04 vs 0·93 ± 0·11 in ACA, P = 0·001) and revealed higher frequency of apoptotic cells (100% vs 9% in ACA, P = 0·001). The USP of ACA-RML showed no diagnostic features of ACC. No differences from ACA were significant, but there was a tendency towards lower dehydroepiandrosterone DHA and DHA metabolites. ACA-RML reveals distinctive histological features and lack of USP markers of malignancy. More cases of this rare tumour may confirm differences from ACA in steroid excretion. It is important to recognize ACA-RML because its size and heterogeneous appearance raise the possibility of ACC.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Penerbit UMT, Universiti Malaysia Terengganu
Date: 31-07-2021
Publisher: Springer Science and Business Media LLC
Date: 21-03-2012
DOI: 10.1245/S10434-012-2306-6
Abstract: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010 :2156-74) derived from a retrospective literature review of 330 patients. This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6 95% confidence interval 2.4-38.4 P < 0.0001), with significantly lower 5-year disease-free survival (χ(2) = 8.7 P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.
Publisher: Elsevier BV
Date: 10-2014
Publisher: Springer Science and Business Media LLC
Date: 14-10-2004
DOI: 10.1007/S00268-004-7671-2
Abstract: Primary hyperparathyroidism (pHPT) is a rare endocrine disease in children and young adults. The widespread use of new developments in pHPT surgery (i.e., unilateral and minimally invasive approaches) is based on the assumption that the solitary adenoma is the predominant intraoperative finding, but it has not been evaluated in the subgroup of young patients. From April 1986 to December 2002, a total of 1219 patients with pHPT have been operated on in our institution. The records of 64 patients (5.3%) younger than 30 years were extracted and compared to those of the older patients. The study group (median age 25 years, range 11-30 years) had significantly less bone pain, fewer signs of bone demineralization, and fewer neuropsychiatric symptoms. Eleven patients had hereditary disease. We found a solitary adenoma in only 32 of the 64 juvenile patients (p < 0.001), multiple gland disease in 25 patients (p < 0.001), and two suspected carcinomas. No adenoma could be identified in five patients. Follow-up of 54 patients after a median of 6.1 years revealed 42 normocalcemic patients, 5 hypocalcemic patients, and 7 patients with hypercalcemia. Altogether, 16 juvenile patients underwent parathyroid reoperations (25%) compared to 105 older patients (9%) (p = 0.003). Problems and difficulties with parathyroid surgery are pronounced in younger patients. The high rate of multiple gland disease requires bilateral cervical exploration as the standard procedure in pHPT patients younger than 30 years of age.
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier BV
Date: 11-2000
Abstract: Coral reef aorta is a rare calcifying disease of the juxtarenal and suprarenal aorta. We report here our surgical experience in treating 21 patients, with a mean follow-up of 4 years and 7 months. Both genders were equally affected. Ten male (48%) and 11 female (52%) patients with a mean age of 54.6 years (range 42-76 years) underwent surgery. The main symptoms were limb claudication (n = 11, 52%), renovascular stenosis (n = 9, 43%) with concurrent renovascular hypertension (n = 5, 24%), and angina abdominalis (n = 7, 33%). Most patients had multiorgan vascular disease such as iliofemoral arterial occlusive disease (n = 14, 66%), coronary artery obstruction (n = 8, 38%), or obstruction of the carotid artery (n = 6, 28%). Risk factors did not differ between coral reef patients and those with other occlusive vascular diseases. All patients were treated through vascular operations, including open thromboendarterectomy of the suprarenal (n = 9, 43%), infrarenal (n = 4, 19%), or supra- and infrarenal aorta (n = 8, 38%), and thromboendarterectomy of the following vessels: celiac artery (n = 7, 33%), superior mesenteric artery (n = 12, 57%), inferior mesenteric artery (n = 3, 14%), unilateral renal artery (n = 3, 14%), or bilateral renal artery (n = 9, 43%). Bypass reconstructions were performed in 39% (n = 8). A thoracoabdominal approach was used in 14 patients (67%) and a median laparotomy in 7 (33%). Our results show that coral reef aorta is not confined to either gender. It appears most frequently in the context of general atherosclerotic disease and patients benefit from timely diagnosis and operation before onset of severe, life-threatening visceral and renal complications.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Georg Thieme Verlag KG
Date: 04-2000
DOI: 10.1055/S-2000-7465
Publisher: The Endocrine Society
Date: 09-2010
DOI: 10.1210/JC.2010-0375
Abstract: Germline missense mutations of the RET protooncogene cause a clinical spectrum called multiple endocrine neoplasia (MEN) type 2. A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance. We report in idualized patient information on 36 carriers of the intracellular RET gene mutation S891A from three centers and clustered data of 38 former patients reported in the literature in nine additional studies. S891A mutation accounts for up to 5% of all patients to date reported with RET mutations and 16% of those hitherto reported with intracellular mutations. S891A mutation caused medullary thyroid cancer (MTC) in 69.4%, pheochromocytoma in 2.8%, and parathyroid hyperplasia in 8.3% of the 36 patients of this case series and in 63.5, 4.1, and 4.1%, respectively, for the entire groups of 74 patients. The youngest age of onset for MTC in this group was 17 yr (median, 46 yr range, 17-80 yr), for pheochromocytoma 46 yr (median, 46 yr), and for parathyroid hyperplasia 17 yr (median, 20 yr, range, 17-46 yr). Persistence of MTC was described in 14.3% of patients with available follow-up. Additional findings included corneal nerve thickening in three of 74 patients (4.1%). This intracellular mutation can initiate the full spectrum of MEN2a, initiates MTC at an early age, and causes recurrence and death if undertreated. We recommend stringent adherence to established guidance in MEN2a in this rare mutation.
Publisher: Elsevier BV
Date: 09-2000
Abstract: We report here a 9-year-old girl with fibromuscular dysplasia of many muscular arteries including both renal and internal carotid arteries, the celiac artery, superior mesenteric artery, and one external carotid artery. She suffered from severe renovascular hypertension with beginning secondary cardiac decompensation, typical angina abdominalis, and neurological signs, including severe headaches and hemianopsia. Surgery was performed for all major vessels and the outcome is good 2.5 years after the operation. The clinical presentation, differential diagnosis, and treatment options of fibromuscular dysplasia in childhood are discussed and the literature is reviewed.
Publisher: Elsevier BV
Date: 08-2023
Publisher: SAGE Publications
Date: 03-2008
DOI: 10.1260/095830508783900744
Abstract: Fear of anthropogenic “global warming” can adversely affect patients' well-being. Accordingly, the state of the scientific consensus about climate change was studied by a review of the 539 papers on “global climate change” found on the Web of Science database from January 2004 to mid-February 2007, updating research by Oreskes, who had reported that between 1993 and 2003 none of 928 scientific papers on “global climate change” had rejected the consensus that more than half of the warming of the past 50 years was likely to have been anthropogenic. In the present review, 31 papers (6% of the s le) explicitly or implicitly reject the consensus. Though Oreskes said that 75% of the papers in her former s le endorsed the consensus, fewer than half now endorse it. Only 7% do so explicitly. Only one paper refers to “catastrophic” climate change, but without offering evidence. There appears to be little evidence in the learned journals to justify the climate-change alarm that now harms patients.
Publisher: Georg Thieme Verlag KG
Date: 09-1998
Abstract: Loss of heterozygosity (LOH) of the MTS1 (p16) tumor suppressor gene has been reported to occur frequently in thyroid cancer cell lines. In order to determine the frequency of LOH for these multiple tumor suppressor genes, we used microsatellite markers IFNA and D9S171 to perform differential quantitative polymerase chain reaction. Tumor DNA was isolated from native sections of tumor tissue. Control DNA was isolated from blood. PCR products were separated on 6% polyacrylamide sequencing gels and quantified according to peak height and area. Analysis was informative in 70% of cases for both markers, and in 88% for at least one out of both. LOH was found in 3 out of 35 informative patients (8.6%) with papillary thyroid cancer, in 1 out of 7 patients with follicular thyroid cancer (14.2%), and in 0 out of 18 medullary cancers (0%). No LOH was found in 11 informative patients with multinodular goitre, 7 with follicular adenoma, 4 with Graves' disease, and 6 with other thyroid disease. 75% of LOH was found in T1 and T2 stages, it was not more frequent in patients with lymphonodular metastasis. The low frequency of LOH in these types of thyroid cancer argues against a role of loss of heterozygosity at the MTS 1 and 2 gene locus in the development of differentiated thyroid neoplasia.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Public Library of Science (PLoS)
Date: 27-04-2021
DOI: 10.1371/JOURNAL.PPAT.1009536
Abstract: Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro , inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.
Publisher: Georg Thieme Verlag KG
Date: 10-2001
DOI: 10.1055/S-2001-17627
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 09-2022
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.4158/EP11184.CR
Publisher: BMJ
Date: 28-10-2011
Publisher: Springer Science and Business Media LLC
Date: 10-1999
Abstract: The frequency of medico-legal issues after surgery is rising. Knowledge of the character and frequency of such problems following surgery of the thyroid gland is scant. Analysis of 21,515 cases of adverse effects after medical treatment from 1975 through 1998 identified 222 cases (1 %) of litigation following surgery for thyroid diseases. The frequency of litigation problems rose exponentially during this interval. Malpractice was confirmed in 36 cases (16 %). The litigation was directed against the surgeon in 95 % of cases, the anesthesiologist in 2 %, both of them in 3 % and the ear-nose-throat surgeon in one case. Eighty-nine percent of the 222 cases occurred after routine thyroid surgery. Typical complications such as recurrent nerve palsy (50 %), hypoparathyroidism (14 %), bleeding (3 %), and late goiter recurrence (1 %) accounted for 63 % of the presumed but for only 31 % of ascertained malpractice cases. Atypical complications such as other neurologic deficits (10 %), infections (5 %), residual nodules (4 %), scar problems (5 %) accounted for 37 % of the suspected but for 70 % of confirmed malpractice cases. Deficiencies in obtaining informed consent were present in only 11 %. Malpractice was more frequently judged to be present, if a second operation was necessary (P < 0.001), if the goal of the operation had been missed (P < 0.001), or if any kind of complication was followed by a fault in postoperative care (P < 0. 001).
Publisher: Elsevier BV
Date: 06-2022
Publisher: Springer Berlin Heidelberg
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 12-04-2021
DOI: 10.1038/S41467-021-22375-X
Abstract: Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a erse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells CD14 + CD1c + monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).
Publisher: Wiley
Date: 03-01-2017
DOI: 10.1002/RMV.1923
Abstract: Langerhans cells (LCs) situated in stratified squamous epithelium of the skin and mucosal tissue are amongst the first cells that sexually transmitted pathogens encounter during transmission. They are potent antigen presenting cells and play a key role in the host mounting an appropriate immune response. As such, viruses have evolved complex strategies to manipulate these cells to facilitate successful transmission. One of best studied ex les is HIV, which manipulates the natural function of these cells to interact with CD4 T cells, which are the main target cell for HIV in which rapid replication occurs. However, there is controversy in the literature as to the role that LCs play in this process. Langerhans cells also play a key role in the way the body mounts an immune response to HSV, and there is also a complex interplay between the transmission of HSV and HIV that involves LCs. In this article, we review both past and present literatures with a particular focus on a few very recent studies that shed new light on the role that LCs play in the transmission and immune response to these 2 pathogens.
Publisher: MDPI AG
Date: 13-04-2020
DOI: 10.3390/RS12081239
Abstract: The exploration of carbonate-hosted Pb-Zn mineralization is challenging due to the complex structural-geological settings and costly using geophysical and geochemical techniques. Hydrothermal alteration minerals and structural features are typically associated with this type of mineralization. Application of multi-sensor remote sensing satellite imagery as a fast and inexpensive tool for mapping alteration zones and lithological units associated with carbonate-hosted Pb-Zn deposits is worthwhile. Multiple sources of spectral data derived from different remote sensing sensors can be utilized for detailed mapping a variety of hydrothermal alteration minerals in the visible near infrared (VNIR) and the shortwave infrared (SWIR) regions. In this research, Landsat-8, Sentinel-2, Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and WorldView-3 (WV-3) satellite remote sensing sensors were used for prospecting Zn-Pb mineralization in the central part of the Kashmar–Kerman Tectonic Zone (KKTZ), the Central Iranian Terrane (CIT). The KKTZ has high potential for hosting Pb-Zn mineralization due to its specific geodynamic conditions (folded and thrust belt) and the occurrence of large carbonate platforms. For the processing of the satellite remote sensing datasets, band ratios and principal component analysis (PCA) techniques were adopted and implemented. Fuzzy logic modeling was applied to integrate the thematic layers produced by image processing techniques for generating mineral prospectivity maps of the study area. The spatial distribution of iron oxide/hydroxides, hydroxyl-bearing and carbonate minerals and dolomite were mapped using specialized band ratios and analyzing eigenvector loadings of the PC images. Subsequently, mineral prospectivity maps of the study area were generated by fusing the selected PC thematic layers using fuzzy logic modeling. The most favorable rospective zones for hydrothermal ore mineralizations and carbonate-hosted Pb-Zn mineralization in the study region were particularly mapped and indicated. Confusion matrix, field reconnaissance and laboratory analysis were carried out to verify the occurrence of alteration zones and highly prospective locations of carbonate-hosted Pb-Zn mineralization in the study area. Results indicate that the spectral data derived from multi-sensor remote sensing satellite datasets can be broadly used for generating remote sensing-based prospectivity maps for exploration of carbonate-hosted Pb-Zn mineralization in many metallogenic provinces around the world.
Publisher: Georg Thieme Verlag KG
Date: 10-2000
Abstract: Activin A belongs to the TGF-beta family of growth factors involved in control of tissue formation by growth inhibition and to a family of hormones involved in human reproduction. Serum levels of dimeric activin A display a sexual dimorphism with significantly higher circulating hormone concentrations in men than in women after menopause. Since goiter is far more frequent in women than in men, we investigated the role of this sex-related growth factor in the human thyroid. Primary cultures were obtained from 3 patients with goiter, and 4 with recurrent goiter. Activin A significantly inhibited the proliferation of human thyroid follicular epithelial cells in vitro in concentrations between 0.5 and 50 ng/ml and was almost as potent as TGFbeta-1. Analysis in native tissues from 12 normal thyroids, 16 goiters, and 5 Graves thyroids demonstrated mRNA expression of the activin subunit betaA, TGFbeta-receptor type I and II, activin receptors type I receptors alk2 and alk4, and activin type II receptors actRII and actRIIb. Isoform analysis of the major functional type I activin receptor alk4 revealed the full-length transcript SKR2-1 and transcripts for the partially truncated proteins SKR2-2 and SKR2-3 in normal thyroids and goiters. Semi-quantitative RT-PCR revealed a significant 2.5-fold decrease of mRNA for alk4-1 type I activin receptors in goiter as compared to normal thyroid (p < 0.05), whereas expression of the type II receptor actRII was unchanged. These data identify a novel growth inhibitory pathway by activin in the human thyroid. Down-regulation of activin receptor type lb in goiter hints towards end-organ changes which could contribute to deficient growth inhibition. These data provide a mechanistic model how the sexually dimorphic hormone activin A may protect males from goitrogenesis.
Publisher: Wiley
Date: 07-12-2011
DOI: 10.1111/J.1365-2265.2011.04162.X
Abstract: Papillary thyroid cancer (PTC) is a common endocrine cancer and commonly presents with lymph node (LN) metastases. The role of surgical removal of the central cervical LN compartment is poorly defined. There are no prospective randomized controlled trials addressing the relevance to the extent of the initial surgical approach. A systematic review of studies of patients with PTC undergoing either prophylactic or therapeutic lymphadenectomy of the central LNs was carried out. Studies involving imaging modalities in the detection of LNs in PTC were also analysed. Twenty-one studies contained data on 4188 patients undergoing prophylactic or imaging-guided removal of the central compartment. Imaging-guided surgery retrieved cancerous central LNs in 346 or 30% of eligible patients, whilst prophylactic central neck dissection yielded histopathological proof of cancer in 898 or 26·2% of patients. Five imaging studies revealed data on the use of ultrasound (US) and/or computerized tomography (CT). The sensitivity of US and CT was poor, ranging from 50% to 70% when accurately calculated. Metastatic central LNs are found in nearly half of all patients with PTC when prophylactic central lymph node dissection (CLND) is performed. With unreliable imaging modalities, prophylactic CLND should be performed on all patients with PTC.
Publisher: Royal College of Surgeons of England
Date: 03-2010
Abstract: We highlight the importance of considering rarer causes of small bowel obstruction in patients presenting after extra-anatomical arterial bypass. Our patient underwent a left common iliac-to-bifemoral bypass extra-anatomical graft for critical limb ischaemia. The patient developed mechanical small bowel obstruction on the 20th postoperative day. Emergency laparotomy revealed incarcerated, obstructed small bowel trapped in the graft tunnel. Recovery was satisfactory following small bowel resection. To the best of our knowledge, small bowel herniation into an arterial bypass graft tunnel, with successful treatment outcome, has not been reported to date.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2014
Publisher: Elsevier BV
Date: 07-2018
Publisher: Georg Thieme Verlag KG
Date: 14-07-2009
Abstract: HGF (hepatocyte growth factor) has been characterised as an important mitogen and motogen in many epithelial cells. The biological and clinical significance of HGF and its receptor c-met in the thyroid is currently under study. Overexpression of c-met is an important feature of papillary thyroid cancer. We developed a quantitative differential RT-PCR method in order to examine HGF-receptor regulation using RNA of about 50 cells per analysis. Experiments were performed in three spontaneously transformed follicular thyroid cancer (FTC) cell lines FTC-133, 236, and 238, 7 primary cultures derived from multinodular goitres, one from Graves disease and 1 from papillary thyroid cancer (PTC). TGF-alpha and to a minor degree HGF were shown to induce a marked up-regulation of the receptor whereas bovine TSH, NaI, dbcAMP or basic FGF had no apparent effect. We conclude that expression of the HGF-receptor is under control of paracrine growth factors activating tyrosine-kinase-dependent pathways. We could demonstrate a minor stimulation of thyroid cell proliferation by HGF in presence but not in absence of 10% fetal calf serum.
Publisher: American Society of Civil Engineers (ASCE)
Date: 04-2018
Publisher: Bioscientifica
Date: 03-2013
Publisher: Elsevier BV
Date: 05-2020
Publisher: American Chemical Society (ACS)
Date: 03-11-2014
DOI: 10.1021/JE500801W
Publisher: Elsevier BV
Date: 04-2017
Publisher: Bioscientifica
Date: 11-2012
DOI: 10.1530/EC-12-0050
Abstract: Cervical lymph nodes (CLNs) are the most common site of metastases in papillary thyroid cancer (PTC). Ultrasound scan (US) is the most commonly used imaging modality in the evaluation of CLNs in PTC. Computerised tomography (CT) and 18 fluorodeoxyglucose positron emission tomography ( 18 FDG PET–CT) are used less commonly. It is widely believed that the above imaging techniques should guide the surgical approach to the patient with PTC. We performed a systematic review of imaging studies from the literature assessing the usefulness for the detection of metastatic CLNs in PTC. We evaluated the author's interpretation of their numeric findings specifically with regard to ‘sensitivity’ and ‘negative predictive value’ (NPV) by comparing their use against standard definitions of these terms in probabilistic statistics. A total of 16 studies used probabilistic terms to describe the value of US for the detection of LN metastases. Only 6 (37.5%) calculated sensitivity and NPV correctly. For CT, out of the eight studies, only 1 (12.5%) used correct terms to describe analytical results. One study looked at magnetic resonance imaging, while three assessed 18 FDG PET–CT, none of which provided correct calculations for sensitivity and NPV. Imaging provides high specificity for the detection of cervical metastases of PTC. However, sensitivity and NPV are low. The majority of studies reporting on a high sensitivity have not used key terms according to standard definitions of probabilistic statistics. Against common opinion, there is no current evidence that failure to find LN metastases on ultrasound or cross-sectional imaging can be used to guide surgical decision making.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1053/GAST.1999.0029900368
Abstract: Lysophosphatidic acid (LPA) is assumed to play an important role in the modulation of injury and tissue repair in nonepithelial tissues. The effects of LPA on intestinal epithelial wound repair in vitro and in vivo were characterized. Effects of LPA on intestinal epithelial restitution and proliferation were assessed by using an in vitro wounding model with confluent intestinal epithelial cell line 6 (IEC-6) monolayers and colorimetric thiazolyl blue (MTT) assays. In addition, LPA signaling pathways were characterized. Effects of LPA on intestinal wound healing in vivo were studied by using the trinitrobenzene model of colitis in rats. LPA significantly enhanced migration and inhibited cell proliferation of IEC-6 cells in vitro. The effects on intestinal epithelial cell migration and proliferation were mediated through transforming growth factor beta (TGF-beta)-independent pathways and binding to a G-protein receptor. In addition, LPA significantly ameliorated intestinal epithelial injury in the trinitrobenzene model of colitis in rats. These findings suggest that LPA enhances intestinal epithelial wound healing by modulation of intestinal epithelial cell migration and proliferation through TGF-beta-independent pathways. Thus, exogenous administration of LPA may provide a new approach for modulating intestinal injury in vivo.
Publisher: Oxford University Press (OUP)
Date: 28-02-2019
DOI: 10.1002/BJS5.50138
Publisher: Springer Science and Business Media LLC
Date: 10-06-2014
DOI: 10.1007/S10151-014-1168-2
Abstract: Clinical research on penetrating injury to the buttock is sparse and largely limited to case reports and clinical series. The purpose of this paper is to provide a detailed overview of literature of the topic and to propose a basic algorithm for management of penetrating gluteal injuries (PGI). MEDLINE, EMBASE, Cochran, and CINAHL databases were employed. Thirty-seven papers were selected and retrieved for overview from 1,021 records. PGI accounts for 2-3 % of all penetrating injuries, with a mortality rate up to 4 %. Most haemodynamically stable patients will benefit from traditional wound care and selective non-operative management. When gluteal fascia injury is confirmed or suspected, a contrast-enhanced CT-scan provides the most accurate injury diagnosis. CT-scan-based angiography and endovascular interventions radically supplement assessment and management of patients with penetrating injury to the major buttock and adjacent extra-buttock arteries. Immediate life-saving damage-control surgery is indicated for patients with hypovolemic shock and signs of internal bleeding. A universal basic management algorithm is proposed. This overview shows that penetrating injury to the buttock should be regarded as a potential life-threatening injury, and therefore, patients with such injuries should be managed in trauma centres equipped with hybrid operating theatres for emergency endovascular and open surgery for multidisciplinary teams operating 24/7.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.SURG.2007.07.040
Abstract: Acute respiratory failure is a common, life-threatening complication after severe trauma. Polymorphisms in cytokine genes, linked to cytokine inducibility, may influence the susceptibility to acute respiratory failure and serve as risk predictors. This PROSPECTIVE cohort study (n = 100) included Caucasian multiple trauma (Injury Severity Score [ISS] >15) patients at a level 1 trauma center in Berlin, Germany. Primary outcome measure acute respiratory failure was defined as a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of 19 being significant risk factors. We conclude that the IL-10 -1082 genotype may be a risk marker for development of acute respiratory failure after trauma.
Publisher: Georg Thieme Verlag KG
Date: 29-06-2020
DOI: 10.1055/A-1182-2016
Abstract: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic affects people around the world. However, there have been striking differences in the number of infected in iduals and deaths in different countries. Particularly, within Central Europe in countries that are similar in ethnicity, age, and medical standards and have performed similar steps of containment, such differences in mortality rates remain inexplicable. We suggest to consider and explore environmental factors to explain these intriguing variations. Countries like Northern Italy, France, Spain, and UK have suffered from 5 times more deaths from the corona virus infection than neighboring countries like Germany, Switzerland, Austria, and Denmark related to the size of their respective populations. There is a striking correlation between the level of environmental pollutants including pesticides, dioxins, and air pollution such as NO2 known to affect immune function and healthy metabolism with the rate of mortality in COVID-19 pandemic in these European countries. There is also a correlation with the use of chlorination of drinking water in these regions. In addition to the improvement of environmental protective programs, there are possibilities to lower the blood levels of these pollutants by therapeutic apheresis. Furthermore, therapeutic apheresis might be an effective method to improve metabolic inflammation, altered vascular perfusion, and neurodegeneration observed as long-term complications of COVID-19 disease.
Publisher: Oxford University Press (OUP)
Date: 17-07-2011
DOI: 10.1634/THEONCOLOGIST.2011-0075
Abstract: After completing this course, the reader will be able to: Describe the centricity and histopathology profiles of each of the three classes of HIV-negative patients identified in this analysis.Correlate nosological classification and outcomes in patients with Castleman's disease. CME This article is available for continuing medical education credit at CME.TheOncologist.com Castleman's disease is a rare primary disease of the lymph nodes with limited available clinical information. A systematic literature search identified 416 cases amenable to detailed analysis. In HIV− patients, centricity, pathology type, the presence of symptoms, gender, and age all predict outcome in univariate analyses. The 3-year disease-free survival (DFS) rate for patients with unicentric hyaline vascular disease (49.5% of cases, class I) was 92.5%, versus 45.7% for those with multicentric plasma cell disease (20.2% of cases, class III) and 78.0% for those with any other combination (22.6% of cases, class II) (p & .0001). HIV+ patients (class IV) exclusively presented with multicentric plasma cell disease and had a 3-year DFS rate of only 27.8%. Kaposi's sarcoma and lymphoma were observed in 59.3% and 9.4% of HIV+ patients and in 2.6% and 3.6% of HIV− patients (p & .0001). Paraneoplastic pemphigus and the syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes were observed exclusively in HIV− patients at a rate of 1.3% and 1.8%, respectively. Clinical, pathological, and viral markers allow for the classification of Castleman's disease into groups with markedly different outcomes and disease associations.
Publisher: Georg Thieme Verlag KG
Date: 16-09-2004
Abstract: Interleukin-1 is a potent pro inflammatory agent, has a direct influence on human thyroid cell function, and modulates cell growth in differentiated thyroid carcinoma cell lines. To evaluate whether a polymorphism on the IL-1beta gene has an influence on the incidence of thyroid disorders, we analyzed the C + 3954 T polymorphism in DNA s les of 673 in iduals. 414 venous blood s les were collected from patients suffering from thyroid diseases (Graves' disease n = 53, euthyroid or hyperthyroid non-immunogenic benign thyroid disorders n = 240, thyroid carcinoma n = 121). 259 persons without thyroid disease served as a control. There was no statistically significant association between either of the thyroid alterations or functional conditions on the one hand and the examined genetic polymorphism on the other. Because of the large number of s les tested we can conclude with a high degree of confidence that there is no association between the genotype and the surveyed diseases.
Publisher: Georg Thieme Verlag KG
Date: 04-2000
DOI: 10.1055/S-2000-7400
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 18-02-1999
Publisher: Springer Science and Business Media LLC
Date: 19-09-2014
DOI: 10.1007/S11883-014-0455-8
Abstract: Bariatric surgery has helped patients attain not only significant and sustained weight loss but has also proved to be an effective means of mitigating or reversing various obesity-related comorbidities. The impressive rates of remission or resolution of type 2 diabetes mellitus (T2D) following bariatric surgery are well documented and have rightly received great attention. Less understood are the effects of bariatric surgery on cardiovascular disease (CVD) and its underlying risk factors. Thanks to the availability of increasingly sensitive laboratory tools, the emerging science of lipidomics and metagenomics is poised to offer significant contributions to our understanding of metabolically induced vascular diseases. They are set to identify novel mechanisms explaining how the varied approaches of bariatric surgery produce the remarkable improvements in multiple organs observed during patient follow-up. This article reviews recent and novel findings in patients through the lens of lipidomics with an emphasis on CVD.
Publisher: Oxford University Press (OUP)
Date: 07-03-2017
Abstract: Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined. However, cells isolated by spontaneous migration are in a mature state, and CD141 cross-presenting DCs (cDC1) are more difficult to define. Different pathogen-binding receptors are susceptible to cleavage by blends of collagenase, demonstrating that great care must be taken in choosing the correct enzyme blend to digest tissue if carrying out pathogen-interaction assays. Finally, we have optimized mononuclear phagocyte culture conditions to enhance their survival after liberation from the tissue.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2010
DOI: 10.1038/NRCLINONC.2010.103
Abstract: Castleman's disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. Histopathology reveals a destroyed lymph node architecture that can range from hyaline-vascular disease to plasma-cell disease. Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. Stage progression of Castleman's disease results from switches between viral latency and lytic replication, and lymphatic and hematogenous spread. Multicentric plasma-cell disease in HIV-1 patients is associated with HHV8 infection. Polyclonal plasmablast proliferation escapes control in the germinal center with eventual malignant transformation into non-Hodgkin lymphoma. Surgery produces excellent results in unicentric disease, while multicentric disease responds to anti-CD20 therapy or IL-6 and chemotherapy. Lymphovascular endothelium and naive B cells are infectious reservoir-opening options for antiangiogenic and anti-CD19 strategies to enhance outcomes in patients with systemic disease.
Publisher: Wiley
Date: 09-2001
Publisher: Elsevier BV
Date: 08-2018
Publisher: The Endocrine Society
Date: 04-2003
Abstract: Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin-secreting parafollicular C cells of the thyroid occurring sporadically and as a component of the multiple endocrine neoplasia type 2/familial medullary thyroid carcinoma syndrome. The primary genetic cause of multiple endocrine neoplasia type 2 is germline mutation of the RET protooncogene. Somatic point mutations in RET also occur in sporadic MTC. Although RET mutation is likely sufficient to cause C-cell hyperplasia, the precursor lesion to MTC, tumor progression is thought to be due to clonal expansion caused by the accumulation of somatic events. Using the genome-scanning technique comparative genomic hybridization, we identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and lifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4) and their ligands glial cell line-derived neurotrophic factor, neurturin, persephin, and artemin that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC.
Publisher: Georg Thieme Verlag KG
Date: 11-07-2014
Abstract: This study analyses new information on gene mutations in paragangliomas and puts them into a clinical context. A suspicion of malignancy is critical to determine the workup and surgical approach in adrenal (A-PGL) and extra-adrenal (E-PGL) paragangliomas (PGLs). Malignancy rates vary with location, family history, and gene tests results. Currently there is no algorithm incorporating the above information for clinical use. A sum of 1,821 articles were retrieved from PubMed using the search terms "paraganglioma genetics". Thirty-seven articles were selected of which 9 were analyzed. It was found that 599/2,487 (24%) patients affected with paragangliomas had a germline mutation. Of these 30.2% were mutations in SDHB, 25% VHL, 19.4% RET, 18.4% SDHD, 5.0% NF1, and 2.0% SDHC genes. A family history was positive in 18.1-64.3% of patients. Adrenal PGLs accounted for 55.1% in mutation (+) and 81.0% in mutation (-) patients (RR 1.2, p < 0.0001). Bilateral A-PGLs accounted for 56.4% in mutation (+) and 3.2% in mutation (-) patients (RR 8.7, p < 0.0001). E-PGL were found in 33.6% of mut+ and 17.3% of mut- (RR 1.7, p < 0.0001). In mutation (+) patients PGLs malignancy varied with location, adrenal (6.4%) thoraco-abdominal E-PGL (38%), H & N E-PGL (10%). Malignancy rates were 8.2% in mutation (-) and lower in mutation (+) PGLs except for SDHB 36.5% and SDHC 8.3%. Exclusion of a mutation lowered the probability of malignancy significantly in E-PGL (RR 0.03 (95% CI 0.1-0.6) p < 0.001). Mutation analysis provides valuable preoperative information to assess the risk of malignancy in A-PG and E-PGLs and should be considered in the work up of all E-PGL lesions.
Publisher: Springer Science and Business Media LLC
Date: 08-2000
Abstract: In a study of growth regulation of the human thyroid gland and thyroid tumors we investigated the impact of iodine and that of the thyroid-specific growth-stimulating hormone TSH. Further studies included locally active growth factors such as the epidermal growth factor, insulin-like growth factor, and tissue transforming growth factors alpha and beta. In addition to studies of growth regulation by the various growth factors in mostly normal thyrocytes, the impact of tumor-specific mutations in oncogenes and tumor-suppressor genes was investigated. The results demonstrated distinct changes in tissue specificity and sensitivity to external stimuli. This rather complex view on thyrocyte growth regulation may be confusing, but it describes the biologic reality more precisely. Increased knowledge of the regulatory processes may lead to the development of new tumor- and patient-specific therapeutic approaches, especially for preventing benign goiter recurrence and for treating follicular and papillary thyroid cancers.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JAUT.2016.05.003
Abstract: Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. DNA of 47 in iduals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.WASMAN.2019.04.029
Abstract: Citrus wastes contain large amounts of pectin as the main constituent in addition to cellulose, lignin and hemicellulose. The thermal degradation behaviors and products distribution from the fast pyrolysis of citrus wastes are different from lignocellulosic biomass due to the high content of pectin. In view of this, the detailed decomposition behaviors of pectin are investigated by using density functional theory (DFT). The calculation results indicate that the most energetically favored initial reaction of pectin is the cleavage of α-1,4-glycoside bond (C
Publisher: SAGE Publications
Date: 10-02-2018
Abstract: To identify the variant features encountered in parathyroid abnormalities and document those suggesting malignant change. Data were collected from a cohort of patients who underwent investigation for primary hyperparathyroidism over a 10-year period. Ultrasonographic features: shape, presence of calcification, cystic changes, heterogeneous echogenicity, vascularity, capsular thickening, local invasion, and vascularity were reviewed retrospectively and were used to correlate with final histological findings. One hundred forty-seven patients with histology and concurrent ultrasonographic scans were reviewed, and ided into benign parathyroid lesions (nodular hyperplasia ( n = 44), adenoma ( n = 93)) and parathyroid carcinoma ( n = 10). Parathyroid carcinomas were significantly larger than benign parathyroid lesions ( P = 0.030). Benign parathyroid lesions showed variant sonographic features: irregular shape (16.8%), heterogenous echogenicity (24.1%), calcification (1.5%), capsular thickening (1.5%), and cystic change (19.7%). A significantly higher proportion of parathyroid carcinomas demonstrated heterogenous echogenicity ( P = 0.022), capsular thickening ( P = 0.023), and infiltrative margin ( P 0.0001) than benign parathyroid lesions. Of the 137 benign parathyroid lesions, 38 (27.7%), 76 (55.5%), 23 (16.8%) were avascular, vascular, and hypervascular, respectively. Of the 10 parathyroid carcinomas, 4 (40%), 3 (30%), and 3 (30%) of lesions were avascular, vascular, and hypervascular, respectively. The vascularity of the lesions did not differ significantly between the parathyroid carcinoma and benign parathyroid lesions ( P = 0.281). Ultrasonographic features such as irregular shape, heterogeneous echogenicity, cystic change, and vascularity are nondiscriminatory features between benign or malignant lesions. Large lesion size together with the presence of calcification, capsular thickening, or infiltrative margin strongly raises the suspicion of a malignant parathyroid lesion, and management should be altered.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Hindawi Limited
Date: 02-2006
DOI: 10.1111/J.1742-1241.2006.00610.X
Abstract: We reported the case of an 85-year-old woman who presented with an acutely tender abdomen and underwent abdominal computed tomography (CT) scanning initially reported as showing erticulitis. After failed conservative management, this patient was taken to theatre, and laparotomy revealed a punctate perforation of the ileum due to a 4 x 3 cm fish fin, which was removed through enterotomy. Retrospective analysis of the initial CT scans showed a foreign body consistent with that removed. This is the first case documented in the literature of perforation of bowel due to fish fin ingestion, as opposed to fish bone. It highlights firstly how common presentations may have an uncommon cause and secondly, how easily a small foreign body can be missed on CT scan. It also highlights and the importance of (i) eliciting a full history of eating habits in those presenting with abdominal pain and (ii) basing intervention on clinical findings. In this case report, we review the wider medical literature on perforation due to foreign body ingestion.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2010
DOI: 10.1007/S00268-010-0722-Y
Abstract: The best surgical approach to parathyroid cancer is disputed. Recommendations vary and are built on incoherent evidence. High rates of recurrence and death require an in-depth review of underlying findings. This retrospective study includes 11 patients with parathyroid cancer who underwent surgery with central and/or lateral neck dissection by a single surgeon between 2005 and 2010. The diagnosis was based on histopathological criteria in all patients. Patterns of lymph node and soft tissue involvement of these and formerly reported patients were analysed based on full-text review of all published cases of parathyroid cancer. In this series only 1 of 11 patients (9.1%) manifested lymph node metastasis. In the literature, lymph node metastases have been reported in only 6.5% of 972 published patients, or in 32.1% of the 196 in whom lymph node involvement was assessed by the authors. They were, with few exceptions, localised in the central compartment. Recurrence in soft tissue is more frequent than in locoregional lymph nodes. Oncological en bloc clearance of the central compartment with meticulous removal of all possibly involved soft tissues, including a systematic central lymph node resection, may improve outcomes and should be included in the routine approach to the suspicious parathyroid lesion. There is no need for a prophylactic lateral neck dissection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2004
Publisher: Oxford University Press (OUP)
Date: 12-2017
DOI: 10.1373/CLINCHEM.2017.277624
Abstract: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates. Corresponding serum assays for most steroid pathway intermediates are usually unavailable because of low demand or lack of immunoassay specificity. Serum steroid analysis by LC-MS/MS is increasingly replacing immunoassay, in particular for steroids most subject to cross-reaction. We developed an LC-MS/MS method for the measurement of serum androstenedione, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, and testosterone. Assay value in discriminating ACC from other adrenal lesions (phaeochromocytoma araganglioma, cortisol-producing adenoma, and lesions demonstrating no hormonal excess) was then investigated. In ACC cases, between 4 and 7 steroids were increased (median = 6), and in the non-ACC groups, up to 2 steroids were increased. 11-Deoxycortisol was markedly increased in all cases of ACC. All steroids except testosterone in males and corticosterone and cortisone in both sexes were of use in discriminating ACC from non-ACC adrenal lesions. Serum steroid paneling by LC-MS/MS is useful for diagnosing ACC by combining the measurement of steroid hormones and their precursors in a single analysis.
Publisher: The Endocrine Society
Date: 2000
Abstract: Adrenal cancer is a rare sporadic disease that has also been observed in the context of multiple endocrine neoplasia type I (MEN I). Adrenal lesions occur in up to 40% of MEN I patients. Loss of heterozygosity of the 11q13 band harboring the menin gene has been reported in more than 50% of patients with adrenal cancer. Despite this high index of suspicion, former screening studies did not reveal mutations of the MEN I gene in 28 patients. We identified loss of heterozygosity of 11q13 microsatellites in five of five patients (100%). In 40%, heterozygosity was retained in codon 418 of the MEN I gene. Complete direct DNA sequencing data of the entire coding region and adjacent splice sites of the MEN I gene were obtained in 14 patients with sporadic adrenal cancer. In only one of them a heterozygous missense mutation, R176Q (exon 3), was identified. Due to the heterozygous pattern and unknown biological effect of this mutation, it is not clear whether there is a causal relationship with adrenal cancer. The total mutation frequency in sporadic adrenal cancer is 1 of 14 (7%). Menin messenger RNA expression was identified in 14 of 14 patients (100%). Transcriptional inactivation of the menin gene is, hence, unlikely to cause loss of its tumor suppressor function in adrenal cancer. Furthermore, we examined three patients who presented adrenal cancer in the context of sporadic multiglandular endocrine tumor disease previously diagnosed on clinical grounds to be MEN I syndrome. An opal stop codon mutation was identified in codon 126 (exon 2) in the adrenal cancer of one of these patients. Formation of the adrenal cancer in this patient may be rather coincidental because the mutation was present in a heterozygous pattern. There was no mutation of the menin gene in the two other patients. This may mean that formation of adrenal cancer in the context of multiglandular endocrine disease denotes an entity different from MEN I in some patients.
Publisher: Royal College of Surgeons of England
Date: 05-2012
DOI: 10.1308/003588412X13171221590052
Abstract: A total of 17 cases of penetrating neck injury were managed by the otolaryngology team at King’s College Hospital over a 3-year period in the 1980s. In April 2010 King’s College Hospital became the major trauma centre for South East London. This prospective cohort study compares the incidence, changing demographic features and treatment outcomes of penetrating neck trauma in South East London over the previous 23 years. Data were collected over a 12-month period (April 2010 to March 2011) and a selective management protocol was introduced to standardise initial investigations and further treatment. The past 23 years have seen a 550% increase in the incidence of penetrating neck injuries in South East London, with a marked increase in gun crime. Only 38% of cases underwent negative neck exploration in 2011 compared with 65% in 1987. Selective conservative management based on the absence of haemodynamic instability or radiological findings reduces length of hospital stay, lightens surgical workload and cuts costs without affecting morbidity or mortality. The increased incidence of penetrating neck injury is a reflection of more interpersonal violence rather than a consequence of the larger South East London trauma centre catchment area. Tackling this problem requires focus on wider issues of community prevention. Sharing of data between the four London trauma centres and the police is needed to help prevent interpersonal violence and develop a universal treatment algorithm for other institutions to follow.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 11-2017
Publisher: Elsevier BV
Date: 04-2019
Publisher: Elsevier BV
Date: 07-2017
Publisher: Springer Science and Business Media LLC
Date: 2001
Abstract: Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inflammatory diseases have been proposed to be the link in such "inflammation-mediated osteopenia." A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically determined difference in the degree of the IL-6 response to stressful stimuli between in iduals. This study aimed to assess the frequency of genotypes and haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further aim was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL-6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bone mineral density was evaluated at baseline and after a prospective 2-year-follow-up. The favorable CC genotype with decreased IL-6 release was not underrepresented in IBD patients compared to healthy controls. Carriage of this genotype was not protective with respect to the development of bone disease, either for the bone mineral density at baseline or for the prospectively observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even slightly higher in CC carriers, but differences did not reach significance. Genetically determined differences in the degree of the IL-6 response to stressful stimuli are no major predictors for the degree of bone disease in IBD patients.
Publisher: Hindawi Limited
Date: 15-05-2019
DOI: 10.1002/ER.4599
Publisher: Elsevier BV
Date: 04-2000
Publisher: Springer Berlin Heidelberg
Date: 2006
Publisher: BMJ
Date: 09-2021
Abstract: We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund’s adjuvant (CFA)) in three preclinical species and in human cancer patients. Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient. Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided. Our data demonstrate that intratumoral injection of CFA has major antitumor effects in a proportion of treated animals and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumors, and is suitable to patients in developing countries and advanced care settings.
Publisher: Springer London
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 19-08-2019
DOI: 10.1002/BJS.11297
Abstract: This study investigated the indications, procedures and outcomes for adrenal surgery from the UK Registry of Endocrine and Thyroid Surgery database from 2005 to 2017, and compared outcomes between benign and malignant disease. Data on adrenalectomies were extracted from a national surgeon-reported registry. Preoperative diagnosis, surgical technique, length of hospital stay, morbidity and in-hospital mortality were examined. Some 3994 adrenalectomies were registered among patients with a median age of 54 (i.q.r. 43–65) years (55·9 per cent female). Surgery was performed for benign disease in 81·5 per cent. Tumour size was significantly greater in malignant disease: 60 (i.q.r. 34–100) versus 40 (24–55) mm (P & 0·001). A minimally invasive approach was employed in 90·2 per cent of operations for benign disease and 48·2 per cent for cancer (P & 0·001). The conversion rate was 3·5-fold higher in malignant disease (17·3 versus 4·7 per cent P & 0·001). The length of hospital stay was 3 (i.q.r. 2–5) days for benign disease and 5 (3–8) days for malignant disease (P & 0·050). In multivariable analysis, risk factors for morbidity were malignant disease (odds ratio (OR) 1·69, 1·22 to 2·36 P = 0·002), tumour size larger than 60 mm (OR 1·43, 1·04 to 1·98 P = 0·028) and conversion to open surgery (OR 3·48, 2·16 to 5·61 P & 0·001). The in-hospital mortality rate was below 0·5 per cent overall, but significantly higher in the setting of malignant disease (1·2 versus 0·2 per cent P & 0·001). Malignant disease (OR 4·88, 1·17 to 20·34 P = 0·029) and tumour size (OR 7·47, 1·52 to 39·61 P = 0·014) were independently associated with mortality in multivariable analysis. Adrenalectomy is a safe procedure but the higher incidence of open surgery for malignant disease appears to influence postoperative outcomes.
Publisher: OMICS Publishing Group
Date: 2014
Publisher: Elsevier BV
Date: 2018
Publisher: Wiley
Date: 2001
DOI: 10.1002/1097-0215(200102)9999:9999<::AID-IJC1166>3.0.CO;2-D
Abstract: Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological activities, e.g., the regulation of cellular proliferation and various aspects of cellular physiology. Signal transduction is achieved by binding to 2 high-affinity receptors, EDG2 and EDG4, and a group of low-affinity receptors, EDG1-7, all belonging to the superfamily of G protein-coupled receptors. We examined the growth-regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary thyroid cancer. We further assessed mRNA expression of high-affinity receptors EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular thyroid cancers and 13 goiters by quantitative RT-PCR. We also identified mRNA expression of phospholipase A(2) and LPA acyltransferase in fresh thyroid tissues derived from various sources. At concentrations of 10, 50 and 150 microM, LPA induced a 2-fold rise of proliferation (p < 0.001) and acted as strongly as thyrotropin. The combination of LPA and TSH produced significant synergistic effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and papillary or follicular thyroid cancer expressed 2 high-affinity cognate LPA receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3-fold in differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression of EDG2 receptor was unchanged in malignancy however, increased EDG2 expression in in idual s les correlated with lymphonodular metastasis (p = 0.01). Thus, lipid mediators are a novel class of factors involved in the control of proliferation in the human thyroid. Altered mRNA expression of the high-affinity LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid cancer.
Publisher: Oxford University Press (OUP)
Date: 2019
DOI: 10.1002/BJS.11051
Abstract: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89·6 per cent) compared with that in countries with a middle (753 of 1242, 60·6 per cent odds ratio (OR) 0·17, 95 per cent c.i. 0·14 to 0·21, P & 0·001) or low (363 of 860, 42·2 per cent OR 0·08, 0·07 to 0·10, P & 0·001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9·4 (95 per cent c.i. −11·9 to −6·9) per cent P & 0·001), but the relationship was reversed in low-HDI countries (+12·1 (+7·0 to +17·3) per cent P & 0·001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0·60, 0·50 to 0·73 P & 0·001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.
Publisher: Bioscientifica
Date: 03-2010
DOI: 10.1677/ERC-09-0191
Abstract: Kidney transplantation and the associated immune suppression are associated with a significantly increased risk of developing cancer during long-term follow-up. Thyroid cancer has been recognised as a potential post-transplant risk but has not yet been subject of a focused review. We therefore performed a meta-analysis on data of 50 861 patients with a total follow-up of 198 595 patient-years and identified a 6.9-fold higher standardised incidence ratio (95% confidence interval 5.6–8.7, P .001) of thyroid cancer post renal transplantation as compared with a non-transplant group. All such cancers were of papillary type as far as histopathology was known. The mean time to discovery was 6.0 years post transplantation. This puts thyroid cancer into the group of high cancer risk following solid organ transplantation which already includes cervical cancer, non-melanoma skin cancer, oral and lip cancer and haematological malignancies. It is unclear what causes the increased cancer incidence. Inclusion of thyroid ultrasound in long-term post-transplant evaluation may help to ensure timely recognition of this condition.
Publisher: Bioscientifica
Date: 12-10-2015
Publisher: Cold Spring Harbor Laboratory
Date: 29-05-2020
DOI: 10.1101/2020.05.26.117408
Abstract: Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a erse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells CD14 + CD1c + CD11c + monocyte-derived dendritic cells and langerin-expressing dendritic cells 2 (DC2).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2003
DOI: 10.1097/00024382-200301000-00004
Abstract: Dysbalance in the immune system is perceived as a major factor for adverse outcome after trauma. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that regulates proliferation, differentiation of cells, wound healing, and angiogenesis. The influence of TGF-beta1 on trauma patients outcome is still unclear. Injury patterns and clinical outcome parameters of 99 consecutive patients with life-threatening injury and an injury severity score (ISS) > 15 were assessed in a prospective, single-center study at a Level I trauma center. Levels of TGF-beta1 in plasma were measured over a 5-day period by an enzyme-linked immunoabsorbant assay (ELISA). TGF-beta1 plasma levels rise shortly after trauma and gradually drop as the 5th day approaches. Mean and maximal TGF-beta1 plasma levels were significantly higher in patients who developed sepsis and were significantly lower in patients with renal or hepatic failure. Receiver operating characteristics-curve analysis of liver failure shows an area under the curve (AUC) of 0.68 (95%: 0.55-0.81, P = 0.02) and of an AUC of 0.63 (95%: 0.52-0.75, P = 0.03) for renal failure for maximal TGF-beta1 plasma (initial until day 2) levels if lower values represent a more positive test. The data indicate that the increase and decrease of TGF-beta1 plasma levels may contribute to clinical outcome after severe injury. Lower TGF-beta1 levels are associated with liver and renal insufficiency. Higher TGF-beta1 levels 6 h after ICU admission increase the risk of sepsis. TGF-beta1 seems to be an early onset reactant and not a second-line responsive cytokine.
Publisher: Wiley
Date: 11-1998
Publisher: Elsevier BV
Date: 09-2011
Publisher: Springer Science and Business Media LLC
Date: 04-2004
DOI: 10.1007/S00268-003-7121-6
Abstract: The object of this study was to assess the extent of surgery required for small sporadic medullary thyroid cancers (sMTCs). We retrospectively studied 261 patients with MTCs treated in our institution between 1986 and 2002 and identified 15 patients with small pT1 or pT2 sMTCs. The tumors were diagnosed incidentally, so surgical therapy was less than total thyroidectomy. Total thyroidectomy with or without neck dissection was applied to all other patients as standard surgical treatment of care. Patients were systematically followed up by postoperative ultrasonography, calcitonin, carcinoembryonic antigen levels, and pentagastrin stimulation tests. On long-term follow-up over a period of 4.6 years, the rate of biochemical cure in these patients who underwent less than total thyroidectomy for a sporadic incidentally diagnosed tumor was 100%. We concluded that completion thyroidectomy and neck dissection are not mandatory in patients in whom a solitary small sMTC is incidentally discovered by histologic diagnosis following operation so long as a genetic background is excluded. Nevertheless, such patients require systematic careful long-term follow-up.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 13-06-2018
DOI: 10.1038/TPJ.2017.24
Abstract: Urinary lipidomics may add new valuable biomarkers to the diagnostic armamentarium for early detection of metabolic and kidney diseases. Sources and composition of urinary lipids in healthy in iduals, however, have not been investigated in detail. Shotgun lipidomics was used to quantify lipidomic profiles in native urine s les from 16 in iduals (eight men, eight women) collected in five fractions over 24 h. All probands were comprehensively characterized by urinary and clinical indices. The mean total urinary lipid concentration per s le was 0.84 μM in men and 1.03 μM in women. We observed significant intra- and interin idual variations of lipid concentrations over time, but failed to detect a clear circadian pattern. Based on quantity and subclass composition it seems very unlikely that plasma serves as major source for the urinary lipidome. Considering lipid metabolites occurring in at least 20% of all s les 38 lipid species from 7 lipid classes were identified. Four phosphatidylserine and one phosphatidylethanolamine ether species (PE-O 36:5) were detectable in almost all urine s les. Sexual dimorphism has been found mainly for phosphatidylcholines and phosphatidylethanolamines. In men and in women urinary lipid species were highly correlated with urinary creatinine and albumin excretion, reflecting glomerular filtration and tubular transport processes. In women, however, lipid species deriving from urinary cells and cellular constituents of the lower genitourinary tract considerably contributed to the urinary lipidome. In conclusion, our study revealed the potential of urinary lipidomics but also the complexity of methodological challenges which have to be overcome for its implementation as a routine diagnostic tool for renal, urological and metabolic diseases.
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Springer Science and Business Media LLC
Date: 16-11-1999
Abstract: Loss of heterozygosity (LOH) on chromosome 11q13 occurs in about 20% of sporadic adrenal neoplasms. Adrenal lesions, mostly benign, occur in up to 40% of patients from MEN I kindreds. The MEN I gene, positioned on 11q13, has been considered a primary candidate gene in these lesions. We studied a group of 15 patients with sporadic adrenal adenoma, and 1 patient with multinodular hyperplasia. Of the 16 patients, 4 had incidentally discovered masses, 5 had Conn's syndrome, 6 suffered from Cushing's syndrome, and 9 had high sex hormone production. Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case. We present complete direct DNA sequencing data of the menin gene in 14 sporadic adrenal adenomas and one with adrenal hyperplasia. We identified one heterozygous missense mutation, T552S, in a hormonally inactive adrenal adenoma. One base exchange was identified close to the intron-exon boundary in intron 9 of a nodular adrenal hyperplasia. mRNA expression studies found that MEN I was transcribed in all 13 s les analyzed. In summary, our study identified the second patient with sporadic benign adrenal tumor presenting a menin gene mutation. Our complete direct sequencing approach adds evidence that menin gene mutations may account only for a minority of benign adrenal tumors if at all. Another tumor-suppressor gene inactivated in sporadic adrenal neoplasms may be located on chromosome 11q13.
Publisher: Wiley
Date: 11-2011
DOI: 10.1111/J.1365-2559.2011.04001.X
Abstract: Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism.
Publisher: Georg Thieme Verlag KG
Date: 05-2000
Abstract: The molecular pathogenesis of adrenal myelolipoma is unclear. Endocrine activity of these tumors and association with other endocrine tumors have stimulated the hypothesis that it may belong to the group of sporadic tumors caused by defects of the gene responsible for multiple endocrine neoplasia type I (MEN-I). DNA of blood and tumoral sections from two patients with adrenal myelolipoma were analyzed by examination of variable number of tandem repeats (VNTR) loci PYGM, D11S987, D11S480, and D11S449 on chromosome 11q13 and by complete direct DNA sequencing of all coding exons and splice junctions of the MEN-I gene. Menin expression was examined by RT-PCR. RT-PCR did not detect menin expression in one adrenal myelolipoma. No loss of heterozygozity on chromosome 11q13 was identified. Intragenic heterozygozity was retained in codon 418 of the menin gene in both patients. No mutation was identified in the coding exons of the menin gene. Complete DNA sequencing yielded no hint that defects of the MEN-I gene are responsible for the formation of adrenal myelolipomas. Adrenal myelolipomas do not share the loss of heterozygozity on chromosome 11q13 observed in some benign adenomatous and many malignant adrenocortical tumors.
Publisher: Elsevier BV
Date: 10-2000
Abstract: Although bone loss and osteoporosis are well-known long-term sequelae of inflammatory bowel disease (IBD), the risk factors for increased bone loss have not been identified. Balances of pro- and anti-inflammatory cytokines influence mechanisms of both chronic inflammation and bone resorption. The aim of this study was to identify genetic risk factors for rapid bone loss in IBD patients as a model of disease- and inflammation-associated bone loss. Multiple clinical parameters, biochemical markers of bone metabolism (vitamin D, parathyroid hormone, N-terminal telopeptide of type-I collagen, desoxypyridinoline, bone alkaline phosphatase), and bone mineral density were prospectively assessed in 83 IBD patients over 1.6+/-0.3 years. Eighty-six healthy bone marrow donors served as controls for allelotyping. The allele status of the interleukin 1 receptor antagonist (IL-1ra), IL-6, heat shock protein 70-2 (hsp 70-2), and heat shock protein 70-hom (hsp hom) genes was typed and correlated with clinical course of IBD and extent of bone loss. The extent of bone loss was not correlated to clinical severity of disease or application of corticosteroids. Noncarriage of the 240-base pair allele of the IL-1ra gene and carriage of the 130-base pair allele of IL-6 were independently associated with increased bone loss. Genetic variations of the hsp genes were not associated with degree of bone loss. The combined presence of the named risk factors was significantly associated with increasing bone loss. Genetic variations in the IL-6 and IL-1ra gene identify IBD patients at risk for increased bone loss.
Publisher: Elsevier BV
Date: 06-2019
Publisher: Mary Ann Liebert Inc
Date: 2001
DOI: 10.1089/10507250150500603
Abstract: Proliferation is controlled by a network of mitogenic and growth inhibitory factors. Transforming growth factor-beta1 (TGF-beta1) and activin A are the most important growth inhibitors of benign follicular epithelial cells of the human thyroid. The effects of these substances on malignant primary thyrocytes are not known. We have examined the growth regulatory effects of activin A and TGF-beta1 in primary cultures derived from four papillary cancers, two follicular thyroid cancers, and three benign thyroid tissues. Malignant cells demonstrated resistance to activin and TGF-beta1 or reversal to a weak but significant mitogenic effect (p < 0.001). We also evaluated the activin receptor transcription pattern. Isoforms alk4-1, 4-2, and 4-3 were found in benign (n = 12) and malignant (n = 22) tissues. Two subtypes of type I and type II activin receptors were demonstrated. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a significant threefold downregulation of alk4-1 receptors in papillary (n = 25) and follicular (n = 18) thyroid cancers as compared to normal thyroids (n = 12) (p < 0.001). To our knowledge these are the first data to demonstrate reversal of activin and TGF-beta1 effects in thyroid malignancy and to demonstrate changes of the type Ib activin receptor expression in thyroid malignancy.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Klaus-Martin Schulte.