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  • 1
    In: Transplantation, 1999, Vol.68(11), pp.1753-1761
    Description: BACKGROUND.: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. METHODS.: One day after liver transplantation, PVG (RT1) into BN(RT1), the rats were infected with rat CMV (RCMV, Maastricht strain; 10 plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. RESULTS.: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-α and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. CONCLUSIONS.: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.
    Keywords: Adjuvants, Immunologic–Pharmacology ; Animals–Pharmacology ; Antiviral Agents–Metabolism ; Cell Adhesion Molecules–Physiology ; Cytomegalovirus–Immunology ; Cytomegalovirus Infections–Virology ; Deferoxamine–Pharmacology ; Graft Rejection–Complications ; Liver–Drug Effects ; Liver Transplantation–Immunology ; Nephritis–Pathology ; Rats–Virology ; Rats, Inbred Bn–Etiology ; Rats, Inbred Strains–Pathology ; Transplantation, Homologous–Metabolism ; Tumor Necrosis Factor-Alpha–Drug Effects ; Virus Replication–Drug Effects ; Adjuvants, Immunologic ; Antiviral Agents ; Cell Adhesion Molecules ; Tumor Necrosis Factor-Alpha ; Deferoxamine;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 2
    Language: English
    In: Acta cytologica, 2018, Vol.62(4), pp.237-243
    Description: The cell block (CB) technique refers to the processing of sediments, blood clots, or grossly visible tissue fragments from cytological specimens into paraffin blocks that can be cut and stained by the same methods used for histopathology. The technique brings additional tissue architectural information. CB can be used for ancillary techniques such as immunocytochemistry and molecular techniques. We reviewed the literature on the various preparatory techniques of CBs. There is a wide range of preparatory techniques for CBs and no golden standard for CBs exists: tens of methods are used in various institutions. The majority of the methods are modified in house techniques with a few commercially available kits. The techniques most commonly used are the plasma/thrombin method, the agar method, and commercially available Histogel- and Cellient CB-methods. Dissatisfaction with the cellular yield of the CBs is common. In the CBs, the cytological material is preserved for future use, which is a tremendous advantage in the era of targeted therapy and biobanking. The CB is thus central to the future of cytology: more can be done with less material and with less invasiveness to the patient.
    Keywords: Cell Block ; Cytology ; Cytology Technique ; Microtomy ; Paraffin Embedding ; Cytodiagnosis -- Methods ; Tissue Fixation -- Methods
    ISSN: 00015547
    E-ISSN: 1938-2650
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  • 3
    Language: English
    In: Surgical endoscopy, July 2012, Vol.26(7), pp.1892-7
    Description: The initial results from ablation therapy for metaplastic/dysplastic Barrett's esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported. Neodymium:yttrium-aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed. At the end of the follow-up period (range, 3-15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1-10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia. The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.
    Keywords: Barrett Esophagus -- Surgery ; Laser Therapy -- Methods
    ISSN: 09302794
    E-ISSN: 1432-2218
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  • 4
    Language: English
    In: The Journal of nutrition, February 2002, Vol.132(2), pp.231-7
    Description: In most hypertensive rat models, serum total cholesterol is typically low and the cholesterol is primarily in the HDL rather than the LDL fraction. This difference from humans usually makes these animals unsuitable for experimental atherosclerosis studies. In the present study, we induced severe hypercholesterolemia including a 10-fold increase in serum LDL cholesterol, endothelial dysfunction and hypertension as well as vascular and renal damage in obese Zucker rats by feeding a human-type high fat, high cholesterol and high salt diet (butter 18, cholesterol 1 and NaCl 6 g/100 g dry weight). Supplementation of this atherogenic diet with plant sterols (1 g/100 g) and replacing the NaCl partially by calcium, magnesium and potassium effectively prevented the diet-induced increases in total and LDL cholesterols and 24-h systolic and mean blood pressures, and markedly improved endothelial function. Plant sterols and the minerals also protected against vascular and renal damage and extended the life span of the obese Zucker rats by 60% compared with the rats fed the atherogenic diet. Our findings suggest that human-type cardiovascular disorders can be induced in obese Zucker rats by feeding a human-type atherogenic diet. This seems to be a suitable animal model for experimental studies on atherosclerosis and hypertension as well as for evaluating new dietary approaches to reducing cardiovascular risk.
    Keywords: Arteriosclerosis -- Diet Therapy ; Cholesterol -- Blood ; Hypertension -- Diet Therapy ; Minerals -- Therapeutic Use ; Obesity -- Diet Therapy ; Phytosterols -- Therapeutic Use
    ISSN: 0022-3166
    E-ISSN: 15416100
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  • 5
    Language: English
    In: The American Journal of Surgery, 2003, Vol.185(2), pp.127-130
    Description: Background We evaluated the prevalence of motion restriction and axillary web syndrome (AWS) after sentinel node biopsy (SNB) and axillary clearance (AC) in a prospective study. AWS is a self-limiting cause of early postoperative morbidity after axillary surgery. Limited range of motion associated with palpable cords of tissue in the axilla are typical for AWS. Methods Altogether 85 breast cancer patients who underwent SNB only (49 patients) or SNB and AC (36 patients) were examined before and after surgery. The range of shoulder flexion and abduction and the presence of AWS were registered. Results The range of shoulder movements was restricted in 24 (45%) patients after SNB only and in 31 (86%) patients who also underwent AC ( P = 0.002). AWS was encountered in 10 (20%) patients with SNB and in 26 (72%) with AC ( P 〈0.00005). Conclusions In the SNB group, significantly less early postoperative morbidity was observed.
    Keywords: Axillary Clearance ; Axillary Web Syndrome ; Breast Cancer ; Postoperative Morbidity ; Sentinel Node Biopsy
    ISSN: 0002-9610
    E-ISSN: 1879-1883
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  • 6
    Language: English
    In: Medical Oncology, 2013, Vol.30(3), pp.1-8
    Description: CIP2A is overexpressed in many cancers, including esophageal squamous cell carcinoma. The regulation of c-MYC and CIP2A expression is characterized by a positive feedback mechanism facilitating the expression of both of them and accelerating cancer cell proliferation in gastric cancer. Increased CIP2A expression is a predictor of poor survival in some cancers. The incidence of positive CIP2A immunostaining and its association with c-MYC and its predictive value in esophageal adenocarcinoma are unknown. All esophageal adenocarcinoma patients from 1990 to 2007 with sufficient material for analysis of CIP2A and c-MYC in two university hospitals were included in the study. In addition, biopsies from Barrett’s epithelium from the cancer patients and control tissue from normal esophageal mucosa adjacent to the tumor were included. CIP2A was moderately or strongly positive in 77.9 %, and c-MYC in 93.8 % of the cancer specimens. These frequencies were statistically different from the expression in normal esophageal epithelium. In addition, there was a positive correlation between CIP2A and c-MYC expression ( p  = 0.018). According to adjusted Cox regression survival analysis, CIP2A and c-MYC had no effect on survival. However, among patients with stage IVA–IVB cancer, there was a trend toward poor prognosis in CIP2A-positive patients. The expression of CIP2A and c-MYC was associated with each other, and their overexpression was found in most cases of esophageal adenocarcinoma. However, CIP2A and c-MYC had no effect on survival.
    Keywords: Esophageal adenocarcinoma ; Prognosis ; Survival ; CIP2A ; c-MYC
    ISSN: 1357-0560
    E-ISSN: 1559-131X
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  • 7
    Language: English
    In: Journal of long-term effects of medical implants, 2002, Vol.12(1), pp.35-52
    Description: Sixteen patients with dislocated ankle fractures fixed between 1988 and 1991 with self-reinforced poly(L-lactide; SR-PLLA) screws and/or rods were followed up after 8.6 to 11.7 years (mean 9.6 years) at the Department of Orthopaedics and Traumatology, Helsinki University Central Hospital. In all patients accurate reduction of the fractures was retained and uneventful bony union was achieved. Good or excellent long-term functional results were observed in 15 out of 16 patients. One patient had post-traumatic osteoarthritis. In 5 patients, a late tissue reaction was observed over an extruding screw head with mild symptoms, which led to removal of small palpable masses. There were two superficial wound infections, one after a primary operation and one caused by a late tissue reaction after an operation. The correct operative technique, where all extruding extraosseous SR-PLLA material should be removed during the primary operation, should be followed.
    Keywords: Absorbable Implants ; Fracture Fixation ; Ankle Injuries -- Surgery ; Fractures, Bone -- Surgery
    ISSN: 1050-6934
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  • 8
    Language: Finnish
    In: Duodecim; laaketieteellinen aikakauskirja, 2010, Vol.126(20), pp.2449-53
    Description: A recommendation for the reporting of thyroid cytological specimens was made as the consensus of the expert meeting arranged by the U.S. National Cancer Institute (NCI). This Bethesda system will replace the former Papa classes also in thyroid cytology. The new Bethesda classification considers the representativeness of the thyroid specimen, and the classification is based on the correlation of the underlying histological change with the cytological report. In particular, follicular tumors and suspicion of them are separated from other tumors into their own group. The new system will bring about a significant improvement to the reports of thyroid cytological specimens.
    Keywords: Biopsy, Fine-Needle -- Standards ; Thyroid Neoplasms -- Classification
    ISSN: 0012-7183
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 9
    Language: English
    In: Endoscopy, 2016, Vol.48(05)
    In: Endoscopy, 2016, Vol.48(05), pp.432-439
    Description: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.
    Keywords: Adult–Diagnosis ; Bile Duct Neoplasms–Epidemiology ; Bile Ducts–Etiology ; Cholangiocarcinoma–Pathology ; Cholangiopancreatography, Endoscopic Retrograde–Pathology ; Cholangitis, Sclerosing–Diagnosis ; Cytodiagnosis–Epidemiology ; Diagnosis, Differential–Etiology ; Early Detection of Cancer–Pathology ; Female–Methods ; Finland–Complications ; Humans–Diagnosis ; Male–Epidemiology ; Middle Aged–Methods ; Retrospective Studies–Statistics & Numerical Data ; Risk Factors–Methods ; Transaminases–Epidemiology ; Transaminases–Analysis ; Transaminases;
    ISSN: 0013-726X
    E-ISSN: 1438-8812
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  • 10
    In: Liver International, May 2012, Vol.32(5), pp.783-789
    Description: BACKGROUNDDetection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult. AIMSThis prospective study aimed to evaluate the role of DNA analysis in combination with brush cytology, scored ERCP findings, and tumour markers to detect hepatobiliary dysplasia and malignancy. MATERIAL AND METHODSBrush samples for cytology and for evaluation of DNA content analysed with flow cytometry came from 102 consecutive PSC patients referred for ERCP. Symptoms, serum Ca19-9 and CEA were determined at the time of index biliary examination. ERCP findings were scored for intra- and extrahepatic changes. The end-points were liver transplantation or diagnosis of malignancy or dysplasia. RESULTSMost of the patients were asymptomatic at the time of ERCP: 73% had no symptoms, and 12% had only mild symptoms. An aneuploid DNA content was evident in 20 (20%) patients, and cells suspected for malignancy in 22 (21%). Seven patients had both aneuploidity and cytology (7%) suspicious for malignancy. An end-point, diagnosis of malignancy or liver transplantation was achieved in 42 patients. Combining DNA ploidity and cytology in patients at the end-point, sensitivity was 72%, specificity 82%, positive predictive value 86% and negative predictive value 67%. DISCUSSION AND CONCLUSIONIn this mostly asymptomatic PSC-patient population, 33% demonstrated abnormal brush cytology or aneuploidity. Determining DNA ploidy and brush cytology during ERCP offers a useful tool for identifying those PSC patients who are at high risk of developing cholangiocancer.
    Keywords: Brush Cytology ; Cholangiocancer ; Dna Content ; Flow Cytometry ; Hepatobiliary Malignancy
    ISSN: 1478-3223
    E-ISSN: 1478-3231
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