24 research outputs found
Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus
Prospective comparative study of spiral computer tomography and magnetic resonance imaging for detection of hepatocellular carcinoma
BACKGROUND: Hepatocellular carcinoma (HCC) is often detected at a
relatively late stage when tumour size prohibits curative surgery.
Screening to detect HCC at an early stage is performed for patients at
risk. AIM: The aim of this study was to compare prospectively the
diagnostic accuracy and classification for management of the two state of
the art secondline imaging techniques: triphasic spiral computer
tomography (CT) and super paramagnetic iron oxide (SPIO) enhanced magnetic
resonance imaging (MRI). PATIENTS: Sixty one patients were evaluated
between January 1996 and January 1998. Patients underwent CT and MRI
within a mean interval of 6.75 days. METHODS: CT and MRI were evaluated
blindly for the presence and number of lesions, characterisation of these
lesions, and classification for management. For comparison of the data on
characterisation, the CT and MRI findings were compared with
histopathological studies of the surgical specimens and/or follow up
imaging. Data of patients not lost to follow up were available to January
2001. RESULTS: SPIO enhanced MRI detected more lesions and overall smaller
lesions than triphasic spiral CT (number of lesions 189 v 124; median
diameter 1.0 v 1.8 cm; Spearman rank's correlation coefficient 0.63,
p<0.001). There was no significant difference in accuracy between CT and
MRI for lesion characterisation. The agreement in classification for
management was very good (weighted kappa 0.91, 95% CI 0.83-0.99).
CONCLUSION: SPIO enhanced MRI detects more and smaller lesions, but both
techniques are comparable in terms of classification for management. SPIO
enhanced MRI may be preferred as there is no exposure to ionising
radiation
Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation
OBJECTIVE: To assess whether diastolic graft function is influenced by
intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in
rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts
were monitored during the first three months after transplantation. The
presence of IL-2 mRNA in endomyocardial biopsies (n = 123) was measured by
reverse transcriptase polymerase chain reaction. To determine heart
function, concurrent M mode and two dimensional Doppler echocardiograms
were analysed. RESULTS: Histological signs of acute rejection
(International Society for Heart and Lung Transplantation (ISHLT)
rejection grade > 2) were strongly associated with IL-2 mRNA expression
(IL-2 mRNA was present in 12 of 20 endomyocardial biopsies (60%) with
acute rejection and in 24 of 103 endomyocardial biopsies (23%) without
acute rejection, p = 0.002). No significant relation was found between
either histology or IL-2 mRNA expression alone and the studied
echocardiographic parameters. However, stratification of the
echocardiographic data into those of patients with and those without acute
rejection showed that during acute rejection IL-2 mR
Differential expression of heme oxygenase-1 and vascular endothelial growth factor in cadaveric and living donor kidneys after ischemia-reperfusion
The extent of graft damage after ischemia-reperfusion reflects the balance
between deleterious events and protective factors. Heme oxygenase-1 (HO-1)
and vascular endothelial growth factor (VEGF) may contribute to
cytoprotection by their anti-inflammatory and antiapoptotic properties.
For investigating whether HO-1 and VEGF play a role in the adaptive
response to ischemia-reperfusion injury after renal transplantation,
kidney biopsies were analyzed from living (n = 45) and cadaveric (n = 16)
donors, obtained at three time points: at the end of cold storage T(-1),
after warm ischemia T(0), and after reperfusion T(+1). The mRNA expression
levels of HO-1, VEGF(165), Bcl-2, Bax, and hypoxia inducible factor-1alpha
were quantified by real-time reverse transcriptase-PCR, and the HO-1 and
VEGF proteins were analyzed by immunohistochemistry. Cadaveric donor
kidneys presented higher mRNA expression levels of hypoxia inducible
factor-1alpha. In contrast, mRNA expression levels of HO-1, VEGF(165), and
Bcl-2 were significantly lower in kidneys from cadaveric donors. Overall,
a significant correlation was observed between mRNA expression of Bcl-2
and VEGF(165), between Bcl-2 and HO-1, and between HO-1 and VEGF(165).
Moreover, protein expression of HO-1 and VEGF was detected in the same
anatomical kidney compartments (glomerulus, arteries, and distal tubules).
Renal function at the first week posttransplantation (analyzed by serum
creatinine levels) showed a significant correlation with both HO-1 and
VEGF mRNA expression, reinforcing the protective role of both genes in the
early events of transplantation. It is concluded that the lower expression
of HO-1, VEGF(165), and Bcl-2 in cadaveric donor kidneys can reflect a
defective adaptation against ischemia-reperfusion injury that may affect
their function in the short term
Intragraft heme oxygenase-1 and coronary artery disease after heart transplantation
Peri-operative tissue injury triggers the development of Transplant Coronary Artery Disease (TCAD). Animal studies have shown that induction of heme oxygenase (HO)-1 protects the donor organ from the development of TCAD. To investigate the role of HO-1 in TCAD after clinical heart transplantation, we measured intragraft mRNA expression of HO-1, HIF-1α, TGF-β, FLIP, and the Bcl-2/Bax balance. Immunohistochemical staining of HO-1 was performed to determine its origin. Myocardial biopsies taken at the end of the transplantation procedure (time 0), at 1 week and at 10 months after transplantation were studied from recipients with or without angiographic signs of accelerated TCAD, diagnosed after 1 year. At time 0, no differences in mRNA expression for any of the measured parameters were found between TCAD positive and negative patients. At 1 week, mRNA expression of HO-1 and TGF-β was higher in grafts that developed accelerated TCAD (p=0.001 and p=0.0002). These higher mRNA levels were accompanied by a pro-apoptotic shift in Bcl-2/Bax (p=0.02), suggesting proneness for apoptosis via the mitochondrial pathway. Immunohistochemical staining showed that HO-1 was mainly produced by infiltrating macrophages. At 10 months, again HO-1 and TGF-β levels were high in TCAD positive patients (p=0.02 and p=0.05), but the expression of apoptotic markers was comparable at this time point. Our results suggest that a higher HO-1 by macrophages in our patient population might be an adaptive response to tissue injury and inflammation, reflecting damage due to the transplantation procedure that finally results in TCAD
Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement
Background and Aims: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (noncirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Methods: Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. Results: After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). Conclusions: The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone
Somatostatin receptor in human hepatocellular carcinomas: Biological, patient and tumor characteristics
Background/Aim: The evidence on the efficacy of somatostatin analogues in the treatment of hepatocellular carcinoma (HCC) in humans is conflicting. A variety of human tumors demonstrate somatostatin receptors. All subtypes bind human somatostatin with high affinity, while somatostatin analogues bind with high affinity to somatostatin receptor subtype 2 (sst2). We investigated the sst2 expression in HCC and examined whether HCCs expressing sst2 are a distinct subgroup. Patients and Methods: Forty-five human HCCs were tested for sst2 expression and biological alterations. The proliferative capacity was determined with Ki67 immunostaining and the DNA ploidy status was measured by fluorescent in situ hybridization with a chromosome 1-specific repetitive DNA probe. Expression of tumor suppressor genes (p16, p53 and Rb1) was measured by immunohistochemistry. Results: sst2 expression was detected in 30 tumors (67%). No correlation existed between sst2 expression and the immunoprofiles of the tumor suppressor genes, aneuploidy, proliferation, age, gender, α-fetoprotein levels, tumor size, tumor grade and underlying liver disease. Conclusion: In 67% of the patients with HCC, sst2 could be detected in the tumor. No clinical, pathological or biological characteristics were specific for sst2-positive tumors. Copyrigh