Histological aspects of coeliac disease and its complications

Mulder, C.J.J. [Promotor]Krieken, J.H. [Promotor

Tendencies in baking quality of common wheat varieties realised in Ukraine and their influence on allele frequency of storage protein genes

Several conditions can mimic the clinical presentation of inflammatory breast cancer. Three women presented with a swollen, red and painful breast which turned out to be inflammatory breast cancer after being treated as infectious mastitis. Non-puerperal bacterial mastitis may be confused with inflammatory breast cancer, leading to potentially preventable delays in diagnosis and treatment. The skin changes in inflammatory breast cancer are caused by tumour emboli within the dermal lymphatics, and not by infiltration of inflammatory cells as is suggested by the nomenclature. Patients who are treated for suspected mastitis without clinical improvement in one week should be referred to outpatient care in the surgery department to exclude underlying malignancy

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis

How long does the average person sleep? Here, Kocevska et al. conducted a meta-analysis including over 1.1 million people to produce age- and sex-specific population reference charts for sleep duration and efficiency.We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including >= 100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (>= 18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (>= 18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST = 9 h in bed, whereas poor sleep quality was more frequent in those spending = 41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.Pathophysiology, epidemiology and therapy of agein

Insulin suppresses bile acid synthesis in cultures rat hepatocytes by down regulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase gene transcription.

Evidence from in vivo studies indicates that the bile acid pool and bile acid excretion are increased in humans with diabetes mellitus and in experimental diabetic animals, and that both parameters return to normal levels after administration of insulin. To investigate the biochemical background of these changes, the effects of insulin on bile acid synthesis and cholesterol 7α-hydroxylase and sterel 27-hydroxylase, two key enzymes in routing of cholesterol toward bile acids, were studied in cultured rat hepatocytes. Mass production of bile acids was dose dependently diminished, showing significant reduction (-33% to -53%) at physiological concentrations of the hormone (1.4 to 14 nmol/L) and a maximal decrease at 140 nmol/L (- 65%). The decrease of bile acid synthesis correlated well with the suppression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity. The enzyme activity for cholesterol 7α-hydroxylase, examined in more detail, was dose dependently diminished on incubation of hepatocytes with various concentrations of insulin, reaching maximal reduction at 14 nmol/L of insulin. Maximal decrease of the enzyme activity was seen after 8 hours of incubation (-70%). Insulin strongly reduced the rise in cholesterol 7α-hydroxylase activity induced by incubation with dexamethasone. Sterol 27- hydroxylase activity was inhibited up to -58% after 24 hours of incubation with 140 nmol/L insulin. To study the mechanism of suppression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity, the effects of insulin on their respective levels of messenger RNA (mRNA) and gene transcription were assessed. The decrease in enzyme activities could be explained by a concomitant reduction in the cholesterol 7α-hydroxylase (-76%) and sterol 27-hydroxylase (-62%) mRNA level. Transcriptional activity, as assessed by nuclear runoff assays, was decreased to the same extent, i.e., -60% for cholesterol 7α-hydroxylase and -75% for sterol 27-hydroxylase. Transient expression experiments using a construct containing the proximal 348 basepairs of the cholesterol 7α-hydroxylase promoter fused to the chloramphenicol acetyltransferase (CAT) gene (-348Rcat) showed a significant reduction of transcriptional activity (-64%) with insulin, indicating that a sequence important for an insulin-induced transcriptional response is located within the first 348 basepairs, preceding the transcription start of the cholesterol 7α-hydroxylase promoter. We conclude that physiological concentrations of insulin suppress bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase gene transcription, and that this effect is mediated through a direct action of the hormone on the hepatocyte. These results may provide an explanation for the increased bile acid pool and excretion as found in humans with untreated diabetes mellitus and in experimental animals with insulin deficiency. Chemicals/CAS: cholesterol 7alpha monooxygenase, 9037-53-0; insulin, 9004-10-8; oxygenase, 9037-29-0, 9046-59-7; sterol 27 hydroxylase, 134712-57-5; Bile Acids and Salts; Chloramphenicol O-Acetyltransferase, EC 2.3.1.28; Cholesterol 7-alpha-Hydroxylase, EC 1.14.13.17; Cytochrome P-450 Enzyme System, 9035-51-2; cytochrome P-450C27/25, EC 1.14.-; Insulin, 11061-68-0; Membrane Glycoproteins; nuclear pore glycoprotein gp210; Nuclear Proteins; RNA, Messenger; Steroid Hydroxylases, EC 1.14.

Evaluation of a panel of expert pathologists: review of the diagnosis and histological classification of Hodgkin and non-Hodgkin lymphomas in a population-based cancer registry

Contains fulltext : 137960.pdf (publisher's version ) (Closed access)Abstract Correct histological classification of malignant lymphomas is important but has always been a difficult challenge. Since 2001 the World Health Organization (WHO) classification has been used, which should make it easier to define distinct disease entities. The purpose of this study was to evaluate the usefulness of a panel of expert hematopathologists in reviewing the diagnosis of malignant lymphomas and to examine whether the discordance between primary and panel diagnoses has declined throughout the years. All patients with a primary malignant lymphoma diagnosed between 2000-2001 and 2005-2006 were identified through the population based cancer registry. All diagnoses were reviewed by a panel of three expert pathologists. In 2000-2001, 344 patients were included, and in 2005-2006, 370 patients. The overall discordance rate decreased from 14% in 2000-2001 to 9% in 2005-2006 (p = 0.06). We were able to identify lymphoma subgroups with the highest discordance rates and lowest discordance rates (mantle cell lymphoma and classical Hodgkin lymphoma), which remained unchanged throughout the years. Based on these results we would propose to review all cases of malignant lymphoma with the exception of mantle cell lymphoma and classical Hodgkin lymphoma, when the initial pathologist has no doubt about the diagnosis

Discrepancies in digital hematopathology diagnoses for consultation and expert panel analysis

Digital pathology with whole-slide imaging (WSI) has a large potential to make the process of expert consultation and expert panel diagnosis more rapid and more efficient. However, comparison with the current methods is necessary for validation of the technique. In this study, we determined if digital assessment of whole-slide images of hematopathology specimens with a focus on the assessment of lymphoma can be used for consultation and panel diagnostics. Ninety-three histological specimens with a suspicion for lymphoma were assessed both with conventional microscopy and digital microscopy with a wash out period between assessments. A consensus diagnosis was based on full concordance between the pathologists or, in case of discordances, was reached at a joint session at a multi-headed microscope. In 81% of the cases, there was a full concordance between digital and light microscopical assessment for all three pathologists. Discordances between conventional microscopy and digital pathology were present in 3% of assessments. In comparison with the consensus diagnosis, discordant diagnoses were made in 5 cases with digital microscopy and in 3 cases with light microscopy. The reported level of confidence and need for additional investigations were similar between assessment by conventional and by digital microscopy. In conclusion, the performance of assessment by digital pathology is in general comparable with that of conventional light microscopy and pathologists feel confident using digital pathology for this subspecialty

Is the sentinel lymph node pathology protocol in breast cancer patients associated with the risk of regional recurrence?

Contains fulltext : 118704.pdf (publisher's version ) (Open Access)BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. METHODS: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. RESULTS: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. CONCLUSION: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D