Myocardial infarction in diffuse large B-cell lymphoma patients - a population-based matched cohort study.

BACKGROUND: The outcome for diffuse large B-cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R-CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. METHOD: We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma-free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population-based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. RESULTS: Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14-1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10-2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01-1.64). Among younger patients (≤70), a short-term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30-day survival among patients and comparators. CONCLUSION: DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.

Uncertain diagnosis and prognosis in advanced melanoma: a qualitative study of the experiences of bereaved carers in a time of immune and targeted therapies.

BACKGROUND: Recent advances in advanced melanoma therapies are associated with improved survival for some patients. However, how patients with diagnoses of advanced disease and their carers experience this expanding treatment paradigm is not well understood. OBJECTIVES: To explore bereaved carers' accounts of the trajectory of advanced melanoma involving treatment by immune or targeted therapies, to build an understanding of their experiences of care relating to diagnosis and prognosis. METHODS: A qualitative exploratory design, using methods drawn from grounded theory, was adopted. Analyses drew on in-depth interviews with 20 bereaved carers from three metropolitan melanoma treatment centres in Australia. A flexible interview guide and structured approach to concurrent data collection and analysis were applied. RESULTS: Carers described qualities of the experience, including the shock of diagnosis after a sometimes-innocuous presentation with vague symptoms. They reported an unclear prognosis with complexity arising from interplay between an uncertain disease trajectory and often ambiguous expectations of outcomes of emerging immune and targeted therapies. Uncertainty dominated carers' experiences, increasing the complexity of care planning. CONCLUSIONS: Effective communication of an advanced melanoma diagnosis and prognosis is critical. Recognition of the uncertainty inherent in the benefit of immune and targeted therapies in a constructive manner may facilitate more timely and effective care-planning conversations between patients, carers and medical specialists.

What is the impact of chronic systemic inflammation such as rheumatoid arthritis on mortality following cancer?

BACKGROUND: Emerging evidence links inflammation and immune competence to cancer progression and outcome. Few studies addressing cancer survival in the context of rheumatoid arthritis (RA) have reported reduced survival without accounting for the underlying mortality risk in RA. Whether this increased mortality is a cancer-specific phenomenon, an effect of the decreased lifespan in RA or a combination of both remains unknown. METHODS: Using Swedish register data (2001-2009), we performed a cohort study of individuals with RA (N=34 930), matched to general population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14 291). Using stratified Cox models, we estimated HRs of death associated with RA in the presence and absence of cancer, by stage and time since cancer diagnosis, for all cancers and specific sites. RESULTS: In the absence of cancer, RA was associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the presence of cancer, the relative effect of RA on mortality was varied by stage. For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative effect of RA on mortality was the same as in the absence of cancer. For cancers diagnosed at advanced stages with absolute higher mortality, the effect decreased (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer diagnosis and were reasonably similar across cancer sites. CONCLUSIONS: Much of the increase in mortality in patients with RA diagnosed with cancer seems to reside with effects of RA independently of the cancer.

Risk of disability pension in patients following rectal cancer treatment and surgery.

BACKGROUND: Aspects of survivorship, such as long-term ability to work, are increasingly relevant owing to the improved survival of patients with rectal cancer. The aim of this study was to assess risk and determinants of disability pension (DP) in this patient group. METHODS: Using Swedish national clinical and population-based registers, patients with stage I-III rectal cancer aged 18-61 years in 1995-2009 were identified at diagnosis and matched with population comparators. Prospectively registered records of DP during follow-up were retrieved up to 2013. Non-proportional and proportional hazards models were used to estimate the incidence rate ratio (IRR) for DP annually and overall. Potential variations in risk by demographic and clinical factors were calculated, with relapse as a time-varying exposure. RESULTS: A total of 2815 patients were identified and compared with 13 465 population comparators. During a median follow-up of 6·0 (range 0-10) years, 23·3 per cent of the relapse-free patients and 10·3 per cent of the population comparators received DP (IRR 2·40, 95 per cent c.i. 2·17 to 2·65). An increased annual risk of DP was evident almost every year until the tenth year of follow-up. Abdominoperineal resection was associated with an increased DP risk compared with anterior resection (IRR 1·44, 1·19 to 1·75). Surgical complications (IRR 1·33, 1·10 to 1·62) and reoperation (IRR 1·42, 1·09 to 1·84), but not radiotherapy or chemotherapy, were associated with risk of DP. CONCLUSION: Relapse-free patients with rectal cancer of working age are at risk of disability pension.

Sick leave and disability pension in Hodgkin lymphoma survivors by stage, treatment, and follow-up time--a population-based comparative study.

PURPOSE: This study seeks to investigate the long-term public health burden of Hodgkin lymphoma (HL) in terms of work loss following contemporary treatment protocols and associations with established treatment complications and lymphoma relapse. METHODS: We identified 1,989 Swedish HL patients (1,082 with clinical information) aged 18-60 (median 33) years at diagnosis 1992-2009, and matched 1:4 to population comparators. Sick leave, disability pension (work loss), and comorbidity were retrieved through September 2013. Relative risks (RR) with 95% confidence intervals (CI) were calculated using Poisson regression, and mean lost work days were estimated yearly during follow-up. RESULTS: The risk of annual work loss was elevated in HL survivors versus comparators up to the 15th year post-diagnosis (RR(5th year) 1.64, 95% CI 1.46-1.84; RR(10th year) 1.33, 95% CI 1.15-1.34; and RR(15th year) 1.30, 95% CI 1.04-1.62). The risk remained elevated up to the 10th year after adjustment for secondary malignancies and cardiovascular disease (RR(10th year) 1.31, 95% CI 1.13-1.52). Advanced-stage patients had more lost days than comparators (mean number(5th year) 66 versus 33, mean difference 34, 95% CI 20-48) as did patients receiving 6-8 chemotherapy courses (62 versus 33, mean difference(5th year) 30, 95 % CI 17-43). Among patients in the first complete remission, a difference was still observed for advanced-stage (51 versus 33, mean difference(5th year) 19, 95% CI 5-34) but not early-stage disease. CONCLUSIONS: Advanced-stage HL survivors treated with full-dose chemotherapy were at increased risk of work loss, not only explained by relapse, secondary malignancies, or cardiovascular disease. IMPLICATIONS FOR CANCER SURVIVORS: The results call for increased awareness and evaluation of reasons for long-term work disability following intensive chemotherapy among young HL survivors.

Posterior cortical brain dysfunction in cognitively impaired patients with Parkinson's disease--a rCBF scintigraphy study.

OBJECTIVES: The aim of the study was to visualize cortical function in Parkinson's patients with various degrees of cognitive impairment. MATERIALS AND METHODS: Thirty-seven patients with Parkinson's disease and three with Parkinson plus syndromes underwent cognitive assessment and rCBF using (99m)TC-HMPAO-SPECT. RESULTS: Almost no regional reductions in cerebral blood flow were seen in patients without cognitive impairment (n = 16). Limited, mainly posterior, blood flow reductions were seen in patients with mild cognitive impairment (n = 14), whereas the reductions were extensive and bilaterally symmetric, involving both anterior and posterior brain regions in patients with dementia (n = 10). CONCLUSIONS: The findings suggest a widespread cortical, mainly posterior type of dysfunction and a relationship between the degree of cognitive impairment and the magnitude of the dysfunction.

Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus.

BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. METHODS: We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. RESULTS: Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.

Sorption Studies of Cobalt(II) on Colloidal Hematite Using Potentiometry and Radioactive Tracer Technique.

The sorption of Co(II) on colloidal hematite was studied as a function of pH, ionic strength, and Co(II) concentration. Two different techniques were used, yielding two different sets of information: (i) potentiometric titrations that provide information on the number of protons released as a function of pH owing to the sorption of Co(II) and (ii) measurement of the amount of cobalt sorbed on the surface as a function of pH using a radioactive tracer, (60)Co. At low Co(II) concentrations (10(-8) M), the sorption was found to be independent of ionic strength but there seems to be a weak ionic strength dependence at higher Co(II) concentrations (10(-4) M). The adsorption edge moved to higher pH with increasing Co(II) concentration. For the high Co(II) concentration, the number of protons released per cobalt sorbed increased from zero to approximately 1.5. The basic charging properties of hematite were modeled with four different surface complexation models. The 1-pK Basic Stern Model (BSM), with binding of electrolyte ions to the Stern plane, seems to be the most reasonable model if the ambition is to describe experimental data at different ionic strengths. The sorption of cobalt was modeled with the 1-pK BSM. By introducing a low concentration of high affinity surface sites for cobalt sorption it was possible to model the sorption in very wide cobalt concentrations, ranging from 10(-8) M to 10(-4) M. Copyright 2000 Academic Press.

ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT.

Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2beta-carboxymethyl-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was performed with six PD patients in whom the [123I]beta-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomatology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [123I]beta-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

Growth hormone induces CCAAT/enhancer binding protein alpha (C/EBPalpha) in cultured rat hepatocytes.

BACKGROUND/AIMS: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transactivator of several genes in the liver, which are regulated by growth hormone. METHODS: Growth hormone (100 ng/ml) was added to primary rat hepatocytes cultured on a laminin-rich matrix. C/EBP mRNA and protein levels were measured by RNase protection assay and Western blotting, respectively. DNA binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Growth hormone treatment for 6 h to 3 days increased C/EBPalpha mRNA levels. Addition of growth hormone for 24 h and 4 days also enhanced the levels of the 42 and 30 kDa isoforms of immunoreactive C/EBPalpha. EMSA showed that addition of growth hormone for 24 h enhanced the abundance of a protein complex binding to a consensus C/EBP binding DNA oligonucleotide. This protein complex was supershifted by antibodies directed against C/EBPalpha but not against C/EBPbeta. There were no consistent effects on C/EBPbeta mRNA or protein at any timepoint. The growth hormone effect on C/EBPalpha expression was not affected by simultaneous incubation with insulin or glucocorticoids, two hormones that previously have been reported to affect C/EBPs. CONCLUSIONS: Growth hormone enhances the levels of C/EBPalpha mRNA and protein as well as the DNA binding activity of C/EBPalpha in cultured rat hepatocytes.

Determination of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione in plasma by direct injection into a coupled column liquid chromatographic system.

The chemical substance 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is in clinical use for the treatment of hereditary tyrosinemia type 1. In the present study, the plasma concentration of NTBC was determined by a coupled column liquid chromatographic method. A 20-microl volume of plasma was diluted with phosphate buffer, pH 2, and injected into a small precolumn (BioTrapAcid C18) with a mobile phase containing sulfuric acid. The precolumn was based on the restricted access principle, i.e., retention of NTBC within the lipophilic pores, while polar and large endogenous compounds were eluted with the void volume. NTBC was transferred to the analytical column using a mobile phase with a high content of acetonitrile. The compound was monitored by UV detection at 278 nm. The standard curve was linear between 0.3 and 69 microM, and the between-day precision (RSD) was 3% (n=6 days) at 13.8 microM and 14% (n=6 days) at 0.3 microM NTBC in plasma. The quantitation limit was approximately 0.3 microM using 20 microl of plasma.

Hepatocyte-stimulated expression of hepatocyte growth factor (HGF) in cultured rat hepatic stellate cells.

BACKGROUND/AIMS: Hepatic stellate cells appear to be the main producers of hepatocyte growth factor of the normal liver. Insulin-like growth factors in doses over 20 ng/ml have been reported to stimulate hepatocyte growth factor production in cultured hepatic stellate cells. The aim of the present study was to investigate whether parenchymal cell conditioned medium had insulin-like growth factor-independent effects on hepatic stellate cells. METHODS: Primary rat hepatic stellate cells were cultured for 1-7 days. DNA synthesis was measured by 3H-thymidine incorporation. Hepatocyte growth factor and transforming growth factor beta1 immunoreactivity was quantified by ELISA. Hepatocyte growth factor mRNA levels were determined with gel RNase protection assay. Parenchymal cell conditioned medium was obtained from hepatocytes cultured for 2 days in medium without added serum or hormones. RESULTS: Incubation of 1-7-day-old hepatic stellate cells for 2 days with parenchymal cell conditioned medium enhanced the medium content of hepatocyte growth factor. Parenchymal cell conditioned medium contained less than 5.0 ng/ml immunoreactive insulin-like growth factor-1 as measured by radio immunoassay. Parenchymal cell conditioned medium did not contain any insulin-like growth factor bioactivity measured as phosphorylation of type 1 insulin-like growth factor receptor beta subunit and a protein with a size consistent with that of insulin receptor substrate-1. The stimulatory effect of parenchymal cell conditioned medium on hepatocyte growth factor was time- and dose-dependent. The effects of a high dose of parenchymal cell conditioned medium (dilution 1:2 containing less than 2.5 ng/ml insulin-like growth factor-1) were additive to that of high doses (100 ng/ml) of insulin-like growth factor-1 or des (1-3) insulin-like growth factor-1, an analogue with low affinity to insulin-like growth factor binding proteins. Neither parenchymal cell conditioned medium nor insulin-like growth factor-1 enhanced transforming growth factor beta1 immunoreactivity in the medium. Both parenchymal cell conditioned medium and insulin-like growth factor-1 stimulated DNA synthesis in hepatic stellate cells, confirming previous reports. CONCLUSIONS: The present results indicate that both insulin-like growth factor-1 and insulin-like growth factor-1-independent factors from hepatocytes can stimulate hepatocyte growth factor production by hepatic stellate cells. Therefore, insulin-like growth factor-1 and other hepatocyte-derived factors may indirectly affect hepatocytes via a paracrine loop.

Quantitative digital evaluation of myocardial exercise thallium-201 single-photon emission tomography in post-menopausal women.

Quantitative computerized analysis of data from myocardial thallium-201 (201Tl) single-photon emission tomography (SPET) may improve the diagnostic accuracy of coronary heart disease. The reference ranges for post-menopausal women are, however, limited and obtained mainly from patients. To compare reference values from healthy post-menopausal women and to improve the quantitative analysis, 20 women (10 patients with coronary heart disease and previous infarction and 10 age-matched healthy volunteers) were examined immediately post exercise and after a delay. A nine-segment 'bull's-eye' model was used for analysis. At visual evaluation, reproducibility was high (93%), no false-positive results were obtained and in 70% of the patients the SPET was interpreted as abnormal. Using reported reference values for quantitative analysis, all the healthy women had an abnormal result. New reference values based on three different methods of 'normalization' were calculated: the relative activity of segment 3 set to 100%, the segment with the highest activity set to 100% and a least-squares method. They all differed significantly from those that had previously been reported. The frequencies of agreement between visual and quantitative analysis were 84-92% and were highest when segment 3 was used as a reference, but in this case only 40% of the patients with coronary heart disease had an abnormal SPET. Using the least-squares method for handling digital information, the SD of the normal values decreased and 90% of the patients with coronary heart disease were accurately diagnosed. These results provide quantitative digital reference values for healthy post-menopausal women. They verify that quantitative analysis is in diagnostic agreement with visual evaluation, stress the need for local verification of reference ranges and suggest a least-square normalization method for the analysis.

Insulin-like growth factors stimulate expression of hepatocyte growth factor but not transforming growth factor beta1 in cultured hepatic stellate cells.

Hepatic stellate cells (HSC) are located adjacent to hepatocytes and produce hepatocyte growth factor (HGF) in the normal liver, whereas transformed HSC in fibrotic livers produce transforming growth factor beta1 (TGFbeta1), an inhibitor ofhepatocyte proliferation. In addition to the endocrine actions of hepatic insulin-like growth factor-I (IGF-I), it also stimulates the proliferation of HSC. In this study we found that addition of IGF-1 (20-500 ng/ml) for 48 h to 2- to 7-day-old primary cultures of rat HSC resulted in a time- and dose-dependent increase by 50-190% of the concentrations of immunoreactive HGF in the medium. The levels of HGF as well as DNA synthesis measured as thymidine incorporation were also enhanced by IGF-II and des(1-3)IGF-I, which has reduced binding to IGF binding proteins. There was no consistent effect of the IGFs on the levels of immunoreactive TGFbeta1 or on the total DNA content of the cultures. There was no effect of human GH on medium levels of HGF or TGFbeta1, thymidine incorporation, or total DNA content. IGF-I increased the abundance of HGF messenger RNA, as measured by the RNase protection/solution hybridization technique, whereas there was no effect on TGFbeta1 or glyceraldehyde phosphate dehydrogenase messenger RNA. The results suggest that IGFs stimulate the production of HGF but not TGFbeta1 by HSC in vitro.

Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA.

The Met protooncogene encodes the tyrosine kinase receptor for the hepatocyte growth factor (HGF), a potent mitogen for hepatocytes and other epithelial cells produced by mesenchymal cells. Many of the studies on the physiologic and neoplastic growth of the liver, as well as other organs, have been performed in the rat. Therefore, chromosomal mapping of the rat Hgf gene and the gene of its receptor is of particular value. To achieve this, a probe of the coding part of rat HGF cDNA was used to isolate four genomic probes from a lambda phage rat genomic library. These probes were used to map the Hgf gene to Chromosome (Chr) 4q12 by the FISH technique. To obtain a probe for the mapping of the HGF receptor/Met gene, we cloned the complete coding region of the rat HGF receptor mRNA. Complementary DNA (cDNA) was synthesized with reverse transcriptase from total RNA for use as a template for the PCR. The two PCR primers were designed based on human and mouse sequences and were located in the flanking regions of the open reading frame of the HGF receptor mRNA. Amplification resulted in a band of an estimated size of 4.1 kb, which was cloned and sequenced. The nucleotide sequence showed about 93% and 85% homology compared with mouse and human HGF receptor sequences, respectively. A full-length probe of the coding part of the cDNA was used to map the rat HGF receptor/Met gene to Chr 4q21 by the FISH technique. Therefore, the rat Hgf and HGF receptor/Met genes are located relatively close to each other, in a way similar to humans but not mice.

The CCAAT/enhancer-binding protein-alpha is expressed in the germinal layer of the growth plate: colocalisation with the growth hormone receptor.

The transcription factor C/EBP alpha, a member of the CCAAT/enhancer-binding protein family, is highly expressed in the liver and in adipose tissue. The aim of this study was to determine if C/EBP alpha is expressed in rat growth cartilage. The expression pattern of C/EBP alpha in monolayer-cultured growth plate chondrocytes was similar to that of C/EBP alpha during hepatocyte and preadipocyte differentiation. Immunohistochemistry with a polyclonal antibody for C/EBP alpha revealed that the C/EBP alpha protein is present in the perichondrial ring, in the germinal layer of the growth plate and on the surface of the articular cartilage. The growth hormone (GH) receptor has a similar distribution in the rat tibial growth plate, and hypophysectomised rats were used to investigate a possible connection between C/EBP alpha and GH. C/EBP alpha mRNA levels were decreased in rib cartilage after hypophysectomy. However, GH treatment did not counteract this effect, indicating that other pituitary hormones regulate the C/EBP alpha mRNA levels in growth plate cartilage. We thus demonstrate, for the first time, that C/EBP alpha is expressed in cartilage. The finding that C/EBP alpha, like the GH receptor, is predominantly expressed in stem cell areas of the rat growth plate indicates a possible functional role for C/EBP alpha during early chondrogenic differentiation.

Changes in expression of CCAAT/enhancer binding protein alpha (C/EBP alpha) and C/EBP beta in rat liver after partial hepatectomy but not after treatment with cyproterone acetate.

BACKGROUND/AIMS: The proliferation rate of adult rat liver is normally very low. It is markedly enhanced during compensatory regeneration, e.g. after partial hepatectomy, or after administration of certain growth promoters, e.g. cyproterone acetate. These two types of liver cell proliferation appear to differ, since the expression of immediate early genes is induced during compensatory regeneration but not after cyproterone acetate treatment. The transcription factor C/EBP alpha, which has been associated with hepatocyte differentiation and growth arrest, is suppressed during compensatory regeneration. In contrast, C/EBP beta, associated with acute phase reaction, is increased during regeneration. We have investigated the effects of the liver growth promoter cyproterone acetate on the hepatic expression of C/EBP alpha and C/EBP beta. METHODS: Adult male rats received either cyproterone acetate treatment or were subjected to partial hepatectomy. Livers were obtained at different time intervals for measurement of C/EBP alpha and C/EBP beta mRNA with solution hybridization/RNAse protection assay, and C/EBP alpha and C/EBP beta content with immunoblotting. RESULTS: The levels of both C/EBP alpha and C/EBP beta mRNA and the corresponding immunoreactivities were unchanged 2-48 h after injection of cyproterone acetate. The levels of C/EBP alpha mRNA and immunoreactivity were significantly suppressed 10-18 h and 18-26 h after partial hepatectomy, respectively. The levels of C/EBP beta mRNA and immunoreactivity were enhanced during compensatory regeneration 2 h after partial hepatectomy. CONCLUSIONS: Liver cell proliferation during regeneration, but not in response to cyproterone acetate treatment, is associated with changes in C/EBP alpha and C/EBP beta expression. This further supports the notion that changes in expression of transcription factors during liver growth in vivo are dependent on the growth inducer.

Is computer-aided interpretation of 99Tcm-HMPAO leukocyte scans better than the naked eye?

In order to compare visual interpretation of inflammation detected by leukocyte scintigraphy with that of different computer-aided quantification methods, 34 patients (25 with ulcerative colitis and 9 with endoscopically verified non-inflamed colonic mucosa), were investigated using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) leukocyte scintigraphy and colonoscopy with biopsies. Scintigrams were obtained 45 min and 4 h after the injection of labelled cells. Computer-generated grading of seven colon segments using four different methods was performed on each scintigram for each patient. The same segments were graded independently using a 4-point visual scale. Endoscopic and histological inflammation were scored on 4-point scales. At 45 min, a positive correlation was found between endoscopic and scan gradings in individual colon segments when using visual grading and three of the four computer-aided methods (Spearman's rs = 0.30-0.64, P < 0.001). Histological grading correlated with visual grading and with two of the four computer-aided methods at 45 min (rs = 0.42-0.54, P < 0.001). At 4 h, all grading methods correlated positively with both endoscopic and histological assessment. The correlation coefficients were, in all but one instance, highest for the visual grading. As an inter-observer comparison to assess agreement between the visual gradings of two nuclear physicians, 14 additional patients (9 ulcerative colitis, 5 infectious enterocolitis) underwent leukocyte scintigraphy. Agreement assessed using kappa statistics was 0.54 at 45 min (P < 0.001). Separate data concerning the presence/absence of active inflammation showed a high kappa value (0.74, P < 0.001). Our results showed that a simple scintigraphic scoring system based on assessment using the human eye reflects colonic inflammation at least as well as computer-aided grading, and that highly correlated results can be achieved between different investigators.