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1.

Background

Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma.

Methodology/Principal Findings

We conducted a laboratory study in a tertiary-care university hospital. Fifty-nine women with histologically proven uterine leiomyoma and ninety-two leiomyoma-free control women have been enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Preoperative serum samples were obtained from all study participants to assay serum thiols, AOPP, protein carbonyls and nitrates/nitrites.Concentrations of serum protein carbonyl groups and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma patients (p<0.001). We found positive correlations between serum AOPP concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683; p=0.021, respectively).

Conclusions/Significance

This study, for the first time, reveals a significant increase of protein oxidative stress status and reduced antioxidant capacity in sera from women with uterine leiomyoma.  相似文献   

2.

Background

Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity.

Results

A label-free mass spectrometry-based strategy was employed for discovery phase analysis of fractionated patient serum samples associated with no or high bone disease. A number of proteins were identified which were statistically significantly correlated with bone disease, including enzymes, extracellular matrix glycoproteins, and components of the complement system.

Conclusions

Enzyme-linked immunosorbent assay of complement C4 and serum paraoxonase/arylesterase 1 indicated that these proteins were associated with high bone disease in a larger independent cohort of patient samples. These biomolecules may therefore be clinically useful in assessing the extent of bone disease.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-904) contains supplementary material, which is available to authorized users.  相似文献   

3.

Introduction

In the work up of primary solid liver lesions it is essential to differentiate correctly between benign and malignant tumors, such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) respectively. A promising new marker to detect HCC is Golgi Protein 73 (GP73). Studies comparing patients with HCC and cirrhosis with normal controls suggested that GP73 is specific for patients with HCC; however, patients with other liver tumors were not included. We therefore studied the predictive value of GP73 in differentiating between solid benign and malignant liver tumors.

Materials and Methods

This study included 264 patients: 88 patients with HCC, 88 with hepatocellular adenoma (HCA), and 88 with focal nodal hyperplasia (FNH). A blood sample was collected from each patient to measure GP73 levels using a quantitative ELISA assay and differences in outcome between subgroups were compared. The receiver operating characteristic (ROC) curve, sensitivity and specificity of GP73 were calculated and compared to alpha-fetoprotein (AFP) levels.

Results

When comparing malignant and benign liver tumors the area under ROC was 0.701 and 0.912 for GP73 and AFP respectively. Test characteristics revealed a sensitivity of 60% for GP73 and 65% for AFP; in addition the specificity was 77% for GP73 and 96% for AFP.

Conclusion

Although the literature suggests that GP73 is a valuable serum marker in patients with HCC, the serum concentration may also be increased in patients with solid benign liver tumors. Therefore, a GP73 assay is less suitable for discriminating between primary malignant and benign tumors of the liver.  相似文献   

4.

Background

Presence of circulating tumor cells (CTC) in patients with metastatic breast, colorectal and prostate cancer is indicative for poor prognosis. An automated CTC (aCTC) algorithm developed previously to eliminate the variability in manual counting of CTC (mCTC) was used to extract morphological features. Here we validated the aCTC algorithm on CTC images from prostate, breast and colorectal cancer patients and investigated the role of quantitative morphological parameters.

Methodology

Stored images of samples from patients with prostate, breast and colorectal cancer, healthy controls, benign breast and colorectal tumors were obtained using the CellSearch system. Images were analyzed for the presence of aCTC and their morphological parameters measured and correlated with survival.

Results

Overall survival hazard ratio was not significantly different for aCTC and mCTC. The number of CTC correlated strongest with survival, whereas CTC size, roundness and apoptosis features reached significance in univariate analysis, but not in multivariate analysis. One aCTC/7.5 ml of blood was found in 7 of 204 healthy controls and 9 of 694 benign tumors. In one patient with benign tumor 2 and another 9 aCTC were detected.

Significance of the study

CTC can be identified and morphological features extracted by an algorithm on images stored by the CellSearch system and strongly correlate with clinical outcome in metastatic breast, colorectal and prostate cancer.  相似文献   

5.

Background

Power morcellation has become a common technique for the minimally invasive resection of uterine leiomyomas. This technique is associated with dissemination of cellular material throughout the peritoneum. When morcellated uterine tumors are unexpectedly found to be leiomyosarcomas or tumors with atypical features (atypical leiomyoma, smooth muscle tumor of uncertain malignant potential), there may be significant clinical consequences. This study was undertaken to determine the frequency and clinical consequence of intraperitoneal dissemination of these neoplasms.

Methodology/Principal Findings

From 2005–2010, 1091 instances of uterine morcellation were identified at BWH. Unexpected diagnoses of leiomyoma variants or atypical and malignant smooth muscle tumors occurred in 1.2% of cases using power morcellation for uterine masses clinically presumed to be “fibroids” over this period, including one endometrial stromal sarcoma (ESS), one cellular leiomyoma (CL), six atypical leiomyomas (AL), three smooth muscle tumor of uncertain malignant potential (STUMPs), and one leiomyosarcoma (LMS). The rate of unexpected sarcoma after the laparoscopic morcellation procedure was 0.09%, 9-fold higher than the rate currently quoted to patients during pre-procedure briefing, and this rate may increase over time as diagnostically challenging or under-sampled tumors manifest their biological potential. Furthermore, when examining follow-up laparoscopies, both from in-house and consultation cases, disseminated disease occurred in 64.3% of all tumors (zero of one ESS, one of one CL, zero of one AL, four of four STUMPs, and four of seven LMS). Only disseminated leiomyosarcoma, however, was associated with mortality. Procedures are proposed for pathologic evaluation of morcellation specimens and associated follow-up specimens.

Conclusions/Significance

While additional study is warranted, these data suggest uterine morcellation carries a risk of disseminating unexpected malignancy with apparent associated increase in mortality much higher than appreciated currently.  相似文献   

6.
Navarro A  Yin P  Monsivais D  Lin SM  Du P  Wei JJ  Bulun SE 《PloS one》2012,7(3):e33284

Background

Uterine leiomyomas, or fibroids, represent the most common benign tumor of the female reproductive tract. Fibroids become symptomatic in 30% of all women and up to 70% of African American women of reproductive age. Epigenetic dysregulation of individual genes has been demonstrated in leiomyoma cells; however, the in vivo genome-wide distribution of such epigenetic abnormalities remains unknown.

Principal Findings

We characterized and compared genome-wide DNA methylation and mRNA expression profiles in uterine leiomyoma and matched adjacent normal myometrial tissues from 18 African American women. We found 55 genes with differential promoter methylation and concominant differences in mRNA expression in uterine leiomyoma versus normal myometrium. Eighty percent of the identified genes showed an inverse relationship between DNA methylation status and mRNA expression in uterine leiomyoma tissues, and the majority of genes (62%) displayed hypermethylation associated with gene silencing. We selected three genes, the known tumor suppressors KLF11, DLEC1, and KRT19 and verified promoter hypermethylation, mRNA repression and protein expression using bisulfite sequencing, real-time PCR and western blot. Incubation of primary leiomyoma smooth muscle cells with a DNA methyltransferase inhibitor restored KLF11, DLEC1 and KRT19 mRNA levels.

Conclusions

These results suggest a possible functional role of promoter DNA methylation-mediated gene silencing in the pathogenesis of uterine leiomyoma in African American women.  相似文献   

7.

Background

Several insertion sites have been described for intraosseous puncture in cases of emergencies when a conventional vascular access cannot be established. This pilot study has been designed to evaluate the feasibility of the mandibular bone for the use of an intraosseous vascular access in a cadaver model.

Methodology/Principal Findings

17 dentistry and 16 medical students participating in a voluntary course received a short introduction into the method and subsequently used the battery powered EZ-IO system with a 15 mm cannula for a puncture of the anterior mandible in 33 cadavers. The time needed to perform each procedure was evaluated. India ink was injected into the accesses and during the anatomy course cadavers were dissected to retrace the success or failure of the puncture. Dental students needed 25.5±18.9(mean±standard deviation)s and medical students 33±20.4 s for the procedure (p = 0.18). Floor of mouth extravasation occurred in both groups in 3 cases. Success rates were 82 and 75% (p = 0.93).

Conclusions/Significance

Despite floor of mouth extravasation of injected fluid into a mandibular intraosseous access might severely complicate this procedure, the anterior mandible may be helpful as an alternative to other intraosseous and intravenous insertion sites when these are not available in medical emergencies.  相似文献   

8.

Introduction

This article reports experience relating to the measurement of orbital volume by means of cone beam computed tomography (CBCT) and Cranioviewer program software in patients who have undergone enucleation and orbital implantation.

Patients and Methods

CBCT scans were made in 30 cases, 10 of which were later excluded because of various technical problems. The study group therefore consisted of 20 patients (8 men and 12 women). The longest follow-up time was 7 years, and the shortest was 1 year. In all 20 cases, the orbital volume was measured with Cranioviewer orbital program software. Slices were made in the ventrodorsal direction at 4.8 mm intervals in the frontal plane, in both bony orbits (both that containing the orbital implant and the healthy one). Similar measurements were made in 20 patients with various dental problems. CBCT scans were recorded for the facial region of the skull, containing the orbital region. The Cranioviewer program can colour the area of the slices red, and it automatically measures the area in mm.

Results

In 5 of the 20 cases, the first 4 or all 5 slices revealed that the volume of the operated orbit was significantly smaller than that of the healthy orbit, in 12 cases only from 1 to 3 of the slices indicated such a significant difference, and in 3 cases no differences were observed between the orbits. In the control group of patients with various dental problems, there was no significant difference between the two healthy orbits. The accuracy of the volume measurements was assessed statistically by means of the paired samples t-test.

Summary

To date, no appropriate method is avaliable for exact measurement of the bony orbital volume, which would be of particular importance in orbital injury reconstruction. However, the use of CBCT scans and Cranioviewer orbital program software appears to offer a reliable method for the measurement of changes in orbital volume.  相似文献   

9.

Objective

To compare horizontal eye positions between proptotic thyroid eye disease patients and normal individuals, and to examine positional changes after orbital decompression surgery in thyroid eye disease patients.

Methods

The present case-controlled and retrospective comparative study included 78 proptotic thyroid eye disease patients who underwent bilateral orbital decompression surgery [lateral orbital wall decompression (Group L), 47 patients; medial orbital wall decompression (Group M), 9 patients; and balanced orbital decompression (Group B), 22 patients] and 143 age-matched healthy volunteers as controls. The interpupillary distance was measured to determine horizontal eye positions before and 3 months after surgery in thyroid eye disease patients and was also examined in control eyes. Horizontal eye shifts were calculated by subtracting postoperative from preoperative interpupillary distances.

Results

Preoperative interpupillary distances in thyroid eye disease patients were significantly larger than in controls. The interpupillary distances were significantly decreased postoperatively in Groups M and B, but were significantly increased in Group L. The order of the magnitude of the horizontal shifts was Groups M>B>L.

Conclusions

Proptotic thyroid eye disease patients preoperatively showed laterally displaced eyes in comparison with controls. However, the eyes shifted medially after the medial orbital wall decompression and the balanced orbital decompression, although the former showed more shift. Medial orbital wall or balanced orbital decompression can be used to correct both lateral and anterior displacement of the eyes.  相似文献   

10.

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA.

Methods

We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity.

Results

WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients'' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients.

Conclusions

We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients.  相似文献   

11.
12.

Background

Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism.

Objective

To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions.

Methods

Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay.

Results

The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction.

Conclusions

Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.  相似文献   

13.

Purpose

To define epidemiological, clinical, therapeutic and prognostic factors influencing survival of breast cancer in young women younger than 35 in southern Tunisia.

Material and methods

This is a retrospective study of 83 patients younger than 35 years and treated within tumors mammary committee of Sfax.

Results

The mean age was 31.7 years. T2 stage, high grade with positive node tumors were frequent. Breast surgery was performed for 73 patients. Chemotherapy was neo-adjuvant, adjuvant and palliative for respectively 10, 62 and 13 patients. Radiotherapy was delivered for 65 patients with curative intent and for 8 metastatic patients. Endocrine therapy was adjuvant in 38 patients and palliative in 6 cases. The overall survival (OS) at 5 years was 66.8%. Pejorative prognostic factors in uni-variate analysis were clinical T stage (T3, T4), and the number of involved lymph nodes.

Conclusion

Despite adequate treatment, the prognosis of breast cancer in young women remains worse. Early diagnosis is necessary to promote outcome.  相似文献   

14.

Objectives

To investigate the effect of phenolic environmental estrogens on uterine leiomyoma from the perspective of clinical epidemiology.

Methods

Urine and blood samples were collected from Han women with uterine leiomyoma and women without uterine leiomyoma, living in Nanjing, China, between September 2011 and February 2013. A total of 156 urine samples and 214 blood samples were collected from the uterine leiomyoma group and 106 urine samples and 126 blood plasma samples from the control group. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentrations were determined by solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Results

Phenolic environmental estrogens in the uterine leiomyoma and control groups were compared based on: gravida>3 and gravida ≤ 3. In participants with gravida>3, urine OP concentration was significantly (P<0.05) higher in the uterine leiomyoma group than in the control group. In participants with gravida ≤ 3, urine NP concentration was significantly (P<0.05) higher in the uterine leiomyoma group compared to controls. Despite obstetric history, urine BPA mean exposure concentration was significantly (P<0.05) different between uterine leiomyoma group and control group. The urine BPA concentration was not significantly (P>0.05) different between gravida>3 and gravida ≤ 3 patients. There was no significant (P>0.05) difference in plasma concentrations of BPA, OP and NP between the leiomyoma group and control group. Mean exposure concentration and range of distribution of BPA, OP and NP plasma concentration differed between the uterine leiomyoma and control group.

Conclusion

Exposure level of phenolic environmental estrogens in human was related with leiomyoma tumorigenesis.  相似文献   

15.

Background

Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases.

Methods

Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed.

Results

The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence.

Conclusion

Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.  相似文献   

16.

Background

We used intensive modern proteomics approaches to identify predictive proteins in ovary cancer. We identify up-regulated proteins in both serum and peritoneal fluid. To evaluate the overall performance of the approach we track the behavior of 20 validated markers across these experiments.

Methodology

Mass spectrometry based quantitative proteomics following extensive protein fractionation was used to compare serum of women with serous ovarian cancer to healthy women and women with benign ovarian tumors. Quantitation was achieved by isotopically labeling cysteine amino acids. Label-free mass spectrometry was used to compare peritoneal fluid taken from women with serous ovarian cancer and those with benign tumors. All data were integrated and annotated based on whether the proteins have been previously validated using antibody-based assays.

Findings

We selected 54 quantified serum proteins and 358 peritoneal fluid proteins whose case-control differences exceeded a predefined threshold. Seventeen proteins were quantified in both materials and 14 are extracellular. Of 19 validated markers that were identified all were found in cancer peritoneal fluid and a subset of 7 were quantified in serum, with one of these proteins, IGFBP1, newly validated here.

Conclusion

Proteome profiling applied to symptomatic ovarian cancer cases identifies a large number of up-regulated serum proteins, many of which are or have been confirmed by immunoassays. The number of currently known validated markers is highest in peritoneal fluid, but they make up a higher percentage of the proteins observed in both serum and peritoneal fluid, suggesting that the 10 additional markers in this group may be high quality candidates.  相似文献   

17.
18.

Background

The aim of this retrospective study was to document the clinical findings and radiological features of idiopathic orbital inflammation syndrome with retro-orbital involvement.

Methods

We searched for ophthalmological patients who received orbital imaging at Zhejiang Provincial People''s Hospital between October 2003 and April 2010. Seventy-three patients were diagnosed with idiopathic orbital inflammation syndrome based on clinicoradiological features, with pathological confirmation of nonspecific inflammatory conditions in 47 patients. Eight patients (11%) had MRI or CT evidence of retro-orbital involvement. All 8 patients were diagnosed with idiopathic orbital inflammation syndrome after biopsy of the orbital lesion. MR images were obtained for all 8 patients; 3 patients also had a contrast-enhanced CT scan.

Results

Seven out of 8 patients with retro-orbital involvement also had orbital apex lesions. Of the 65 patients without retro-orbital involvement, 19 had orbital apex lesions. The difference in the number of patients with orbital apex lesions between the two populations was significant (Fisher exact test P = .002). In all 8 patients with retro-orbital involvement, the inflammation spread through the superior orbital fissure. The retro-orbital lesions were isointense to grey matter on T1-weighted images, hypointense on T2-weighted images, and displayed uniform contrast enhancement; on contrast-enhanced CT scans, they were hyperdense relative to the contralateral mirror area and had radiological contours that were similar to those seen on MR images. The diffuse inflammation with marked sclerosis and hyalinization that we observed in the patients with retro-orbital involvement is consistent with the diagnosis of the sclerosing subtype of idiopathic orbital inflammation syndrome. All 8 patients also complained of mild to moderate periorbital pain (headache).

Conclusions

In patients with idiopathic orbital inflammation syndrome, it is important to perform MRI and CT scans to identify possible retro-orbital involvement. Retro-orbital involvement is more frequent when the lesion is present in the orbital apex.  相似文献   

19.

Background

Immune-related pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated bone marrow destruction or suppression. The bone marrows of IRP patients have remarkably increased erythroblastic islands (EIs).

Methodology and Principal Findings

We determined the immunoglobulin G (IgG) autoantibodies in some parts of EIs of IRP patients using immunofluorescence to investigate the biological function of EIs with IgG in the pathophysiology of IRP. The dominant class of autoantibodies detected in mononuclear cells was IgG (CD34 IgG, CD15 IgG, and GlycoA IgG), specifically IgG on GlycoA-positive cells (GlycoA IgG). Results show that extravascular hemolysis occurred in IRP through IgG autoantibodies in the EIs. These data included a high percentage of reticulocytes in the peripheral blood, hypererythrocytosis in the bone marrow, and high serum bilirubin. Furthermore, we examined the macrophages in the bone marrow of IRP patients. The results show that the number of activated macrophages relatively increased, and the phagocytic activity of macrophages significantly increased.

Conclusions and Significance

Increased EIs with IgG were the sites of erythroblast phagocytosis by the activated macrophages, rather than erythropoietic niches. The IgG autoantibodies in the EIs possibly functioned as adhesion molecules for a ring of erythroblasts around the macrophages, thereby forming morphologic EIs.  相似文献   

20.

Background

Base of tongue (BOT) is a difficult subsite to examine clinically and radiographically. Yet, anatomic delineation of the primary tumor site, its extension to adjacent sites or across midline, and endophytic vs. exophytic extent are important characteristics for staging and treatment planning. We hypothesized that ultrasound could be used to visualize and describe BOT tumors.

Methods

Transcervical ultrasound was performed using a standardized protocol in cases and controls. Cases had suspected or confirmed BOT malignancy. Controls were healthy individuals without known malignancy.

Results

100% of BOT tumors were visualized. On ultrasound BOT tumors were hypoechoic (90.9%) with irregular margins (95.5%). Ultrasound could be used to characterize adjacent site involvement, midline extent, and endophytic extent, and visualize the lingual artery. No tumors were suspected for controls.

Conclusions

Ultrasonography can be used to transcervically visualize BOT tumors and provides clinically relevant characteristics that may not otherwise be appreciable.  相似文献   

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