[Assessment of physicians with a foreign diploma; results of 10 years of testing of physicians with a foreign diploma]. / Toetsing van artsen met een buitenlands diploma.

OBJECTIVE: To determine the result of the assessment procedure, initiated on 1 December 2005, for physicians with a foreign diploma who wish to practice in the Netherlands. DESIGN: Retrospective, descriptive study. METHOD: The Commission for Foreign Healthcare Graduates (CBGV) collected data on physicians with a foreign diploma who followed the procedure for requesting a declaration of professional competence and admission to the Dutch Individual Healthcare Professions (BIG) register between December 2005 - December 2015. The procedure comprises a language and communication test, followed by tests of professional competence. On the grounds of the test results, the CBGV can decide if a physician should follow a specific training course. The number of physicians who ultimately obtained BIG registration was determined. RESULTS: During the study period, 183 of the 206 physicians with a foreign diploma passed the general knowledge and skills tests. A total of 176 of the 183 physicians took the professional competence tests. In 43 (25%) of them no shortcomings in knowledge and skills were seen. They were registered in the BIG register for a period of supervision. In 129 (73%), shortfalls were made up by means of focused training programme. In 4 (2%) of them no training was possible. On the date of assessment, 137 (78%) physicians were registered. This number is expected to rise to 151 (86%). CONCLUSION: The provision of a further course of training that is focused on the elimination of identified shortcomings in physicians with a foreign diploma, increases the percentage of foreign physicians that are successfully admitted to the BIG register.

[Hypertension due to fibromuscular dysplasia: look for additional disease sites]. / Hypertensie door fibromusculaire dysplasie.

Fibromuscular dysplasia (FMD) is a non-inflammatory, non-atherosclerotic vasculopathy that can lead to arterial stenosis, occlusion, aneurysms, and dissection. FMD of the renal arteries can lead to renovascular hypertension. Percutaneous angioplasty of the renal arteries (PTRA) can lead to normalization of blood pressure in 45% of patients with renal artery stenosis caused by FMD, particularly in younger patients and patients with a short history of hypertension. A considerable number of the patients with renovascular FMD also have cervical FMD, which can lead to ischaemic or haemorrhagic stroke. In this article we discuss diagnostic and therapeutic options, illustrated by two cases of patients with renovascular and carotid FMD. Most of the recommendations are based on data from retrospective studies and expert opinion; prospective studies on the optimal diagnostic strategy and treatment are therefore, urgently required.

Reliability and validity of an extended clinical examination.

INTRODUCTION: An extended clinical examination (ECE) was administered to 85 final year medical students at the Radboud University Medical Centre in the Netherlands. The aim of the study was to determine the psychometric quality and the suitability of the ECE as a measurement tool to assess the clinical proficiency of eight separate clinical skills. METHODS: Generalizability studies were conducted to determine the generalizability coefficient and the sources of variance of the ECE. An additional D-study was performed to estimate the generalizability coefficients with altering numbers of stations. RESULTS: The largest sources of variance were found in skill difficulties (36.18%), the general error term (26.76%) and in the rank ordering of skill difficulties across the stations (21.89%). The generalizability coefficient of the entire ECE was above the 0.70 lower bound (G = 0.74). D studies showed that the separate skills could yield sufficient G coefficients in seven out of eight skills, if the ECE was lengthened from 8 to 14 stations. DISCUSSION: The ECE proved to be a reliable clinical assessment that enables examinees to compose a clinical reasoning path through self-obtained data. The ECE can also be used as an assessment tool for separate clinical skills.

The prevalence of renal artery stenosis among patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) have a high prevalence of atherosclerotic vascular lesions. It is therefore reasonable to assume that also the rate of renal artery stenosis (RAS) is higher. The presence of a RAS can have implications for the treatment of patients with diabetes mellitus and hypertension and renal impairment. Therefore it is important to be informed about the chance that a RAS is present among such patients. METHODS: We prospectively studied the prevalence of atherosclerotic renal artery stenosis (RAS) among patients with diabetes mellitus. Patients were included if they were diagnosed with DM and hypertension with or without impairment of renal function. If causes of renal disease other than DM or hypertension were more probable on the basis of biochemical data, then such patients were excluded. A magnetic resonance angiography (MRA) of the renal arteries was made in 54 included successive patients. PATIENT CHARACTERISTICS: mean age 59 ± 8.5 years (range 35 to 80). Eight patients had DM 1 and 46 DM 2. Mean BMI was 31.4 ± 5.6 kg/m(2). A RAS was present in 18 of the 54 (33%) patients, 3 patients had bilateral stenoses. Factors related to the presence of RAS were diastolic blood pressure, glomerular filtration rate and dyslipidaemia. CONCLUSION: In this group of diabetic patients with hypertension and or renal impairment the prevalence of RAS was 33%.

Clinical significance of low-grade renal artery stenosis.

BACKGROUND: Patients with a renal artery stenosis (RAS) >50% carry an increased risk for future cardiovascular (CV) events. Experimental literature on this topic suggests that this might as well be true for subjects with lower-grade RAS. METHODS: Recruitment in this longitudinal cohort study was conducted from 1982 to 2002 in a Dutch University Hospital. Included in this study were 301 hypertensive patients clinically suspected of having RAS. Study participants were radiologically classified as having no, a low-grade (<50% lumen narrowing) or high-grade (> or =50%) RAS. A predetermined composite CV end-point was defined as one of the following: myocardial infarction or 'objectified' angina pectoris, ischaemic stroke or death from any CV cause. Other end-points were the occurrence of CV complications, all-cause plus CV mortality and decline in renal function. RESULTS: During a median follow-up of 8.2 years, the incidence of the composite end-point totalled 79 events. After full adjustment in Cox models, a significant risk increase in high-grade [hazard ratio (HR) 2.81; P = 0.002] and low-grade RAS (HR 2.32; P = 0.038) was observed. Other end-points did not differ significantly between study groups. CONCLUSION: Hypertensive subjects with RAS of any extent, compared with hypertensives without RAS, carry a substantially increased risk for future CV events. Therefore, even in patients with low-grade RAS, aggressive pharmacological treatment strategies should be adopted as a preventive measure.

MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.

BACKGROUND: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression. METHODS: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available. RESULTS: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found. CONCLUSION: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

DNA copy number profiles of primary tumors as predictors of response to chemotherapy in advanced colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is biologically a heterogeneous disease, which may affect response to drug therapy. We investigated the correlation of genome-wide DNA copy number profiles of primary tumors with response to systemic chemotherapy in advanced CRC. PATIENTS AND METHODS: DNA was isolated from formaldehyde-fixed paraffin-embedded primary tumors of 32 patients with advanced CRC, which were selected based on either a good response (n = 16) or a poor response (n = 16) to first-line combination therapy with capecitabine and irinotecan. High-resolution DNA copy number profiles were obtained by means of 30 K oligonucleotide-based array comparative genomic hybridization (aCGH). RESULTS: Unsupervised hierarchical cluster analysis of the aCGH data revealed two clusters of 19 and 13 tumors, respectively, and cluster membership showed a significant correlation with response status (P < 0.03). The nonresponders had fewer chromosomal alterations compared with the responders, in particular less losses were found (P < 0.03). Most prominent differences between the two groups were losses of regions 18p11.32-q11.2 (P < 0.02) and 18q12.1-q23 (P < 0.03), which were more frequently observed in responders. CONCLUSIONS: Differences in DNA copy number profiles of primary CRCs are associated with response to systemic combination chemotherapy with capecitabine and irinotecan. Responders overall had more chromosomal alterations, especially loss of chromosome 18.

Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression.

OBJECTIVE: This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon. METHODS: Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays. RESULTS: The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q. CONCLUSION: This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.

The effect of arginine vasopressin on endothelin production in the human forearm vascular bed.

OBJECTIVES: To study whether arginine vasopressin (AVP) can stimulate endothelin production and/or release in vivo, in the human forearm vasculature. DESIGN: The effect of the infusion of AVP into the brachial artery on endothelin production across the human forearm vascular bed was studied in healthy male volunteers, and was compared with intra-arterial infusion of placebo. In another group the effects of AVP on endothelin production were studied after a prior infusion of L-NG-monomethyl-arginine (L-NMMA), a nitric oxide-synthase inhibitor. In a fourth group the effect of L-NMMA alone, without AVP infusion, on endothelin production was studied. METHODS: We measured the effects of AVP, placebo, L-NMMA followed by AVP and L-NMMA followed by placebo on arterial and venous endothelin concentrations in the forearm of four groups, each consisting of five healthy male volunteers. Forearm blood flow was measured by strain gauge plethysmography. The endothelin production was calculated as forearm blood flow times (venous - arterial) endothelin concentration. RESULTS: The group infused with L-NMMA followed by infusion of 8 ng AVP/min per dl forearm volume showed a significant rise in endothelin production from 1.3 (1.8) to 5.0 (2.0) pg/min/dl at 15 minutes (p<0.05, ANOVA). This rise in endothelin production was also significantly different from the endothelin production at 15 minutes in the other three groups (p<0.01, ANOVA). CONCLUSION: In healthy male volunteers intra-arterial infusion of AVP induced a rise in endothelin production in the forearm within 15 minutes, but only after prior infusion of L-NMMA. This observation suggests that the AVP-induced production of nitric oxide offsets AVP-mediated release of endothelin.

Chromosomal instability in flat adenomas and carcinomas of the colon.

Flat adenomas are flat or slightly elevated dysplastic lesions of the colorectal mucosa, mostly with a tubular architecture. Compared with polypoid adenomas of similar size, flat adenomas show a higher frequency of high-grade dysplasia and rapid submucosal invasion. The aim of this study was to survey whether flat colorectal lesions differ in their pattern of chromosomal aberrations from their polypoid counterparts. Six flat adenomas and 12 flat carcinomas were analysed by comparative genomic hybridization (CGH) and the pattern of chromosomal aberrations was compared with a previously published series of 112 polypoid adenomas and 82 polypoid carcinomas. In addition, multiplex ligation-dependent probe amplification (MLPA) for identifying DNA copy number changes of 25 individual genes on chromosome 20 was performed on 14 flat and 15 polypoid tumours. With CGH, flat adenomas showed on average 1.8 gains (range 1-4) and 3.2 losses (range 0-4), and the flat carcinomas 4.5 gains (range 0-8) and 3.5 losses (range 1-6). In both adenomas and carcinomas, high frequencies of 20q gain (83% and 92%, respectively) and 18q loss (83% and 92%, respectively) were found. This correlation between 20q gain and 18q loss had previously been observed in a subgroup of polypoid colorectal tumours. Both flat and polypoid colorectal tumours with 20q gains by CGH showed similar patterns of copy number ratios for the individual genes tested. TOP1, BCL2L1, and E2F1 had median copy number ratios of 2 or higher, while ZNF217 had a ratio around 3. In conclusion, flat adenomas and carcinomas of the large intestine show a similar pattern of chromosomal aberrations to that observed in a specific subgroup of polypoid lesions. The transcription factor ZNF217 is an important candidate for driving the 20q gain.

The structure of medical competence and results of an OSCE.

BACKGROUND: Medical competence is a central concept in medical education. Educational efforts in medical training are directed at the achievement of a maximal medical competence. The concept of the structure of medical competence (multidimensional or one-dimensional with strongly interrelated competences) therefore affects the educational developments and assessment procedures. PURPOSE: To examine the applicability of a one or more dimensional character of medical competence in student assessments, by analysing the results of 356 students in the history taking station of an objective structured clinical examination (OSCE), in relation to other assessment procedures. METHODS: The performances of 356 students in a history taking station of an OSCE were analysed. Analyses of the checklist scores were aimed at the dimensionality of history taking skills. External criteria were used to test the validity of the scores on the checklist. RESULTS: The analyses of the scores on the history taking checklist indicated at least five dimensions of history taking skills: the frequency of patient-centred skills, the quality of performance of patient-centred skills, complaint-oriented skills, general social skills, and the provision of procedural information. CONCLUSION: Medical competence, as a subject of assessment, can be seen as a multifaceted construct. This study shows that history taking alone might be composed of five different dimensions, suggesting that medical competence in respect of assessment might be viewed as a multifaceted construct which in that sense has implications for the assessment of medical competence.

Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach.

BACKGROUND: Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of the mechanisms of progression from a preneoplastic condition through intraepithelial neoplasia to invasive cancer may provide information relevant to designing focused prevention strategies. METHODS: Because the pattern of chromosomal aberrations in precursors of gastric cancer is unclear, 11 gastric polyps with intraepithelial neoplasia (three hyperplastic polyps and eight adenomas) were analysed by microarray comparative genomic hybridisation to study chromosomal instability in precursors of gastric cancer. RESULTS: Chromosomal aberrations were detected in all specimens. Adenomas showed no more chromosomal aberrations than did the hyperplastic polyps. The most frequent aberrations were gain of 7q36 and 20q12, and loss of 5q14-q21 in the adenomas, and loss of 15q11-14, 1p21-31, and 21q11-21.2 in the hyperplastic polyps. The most frequent chromosomal aberration in common to both types was loss of 9p21.3. CONCLUSION: Hyperplastic polyps showed many chromosomal aberrations, confirming that neoplastic transformation can occur in these lesions. These observations are consistent with the existence of two morphologically and genetically distinct pathways to gastric cancer-the hyperplastic polyp pathway and the (intestinal type) adenoma pathway. The relative contribution of each to gastric carcinogenesis in general, and how they compare to patterns of chromosomal aberrations in the more prevalent flat foci of intraepithelial neoplasia remain to be determined.

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Resistance to antihypertensive medication as predictor of renal artery stenosis: comparison of two drug regimens.

BACKGROUND: Renal artery stenosis is among the most common curable causes of hypertension. The definitive diagnosis is made by renal angiography, an invasive and costly procedure. The prevalence of renal artery stenosis is less than 1% in non-selected hypertensive patients but is higher when hypertension is resistant to drugs. OBJECTIVE: To study the usefulness of standardised two-drug regimens for identifying drug-resistant hypertension as a predictor of renal artery stenosis. DESIGN AND SETTING: Prospective cohort study carried out in 26 hospitals in The Netherlands. PATIENTS: Patients had been referred for analysis of possible secondary hypertension or because hypertension was difficult to treat. Patients < or =40 years of age were assigned to either amlodipine 10 mg or enalapril 20 mg, and patients >40 years to either amlodipine 10 mg combined with atenolol 50 mg or to enalapril 20 mg combined with hydrochlorothiazide 25 mg. Renal angiography was performed: (1) if hypertension was drug-resistant, ie if diastolic pressure remained > or =95 mm Hg at three visits 1-3 weeks apart or an extra drug was required, and/or (2) if serum creatinine rose by > or =20 micromol/L (> or =0.23 mg/dL) during ACE inhibitor treatment. RESULTS: Of the 1106 patients with complete follow-up, 1022 had been assigned to either the amlodipine- or enalapril-based regimens, 772 by randomisation. Drug-resistant hypertension, as defined above, was identified in 41% of the patients, and 20% of these had renal artery stenosis. Renal function impairment was observed in 8% of the patients on ACE inhibitor, and this was associated with a 46% prevalence of renal artery stenosis. In the randomised patients, the prevalence of renal artery stenosis did not differ between the amlodipine- and enalapril-based regimens. CONCLUSIONS: In the diagnostic work-up for renovascular hypertension the use of standardised medication regimens of maximally two drugs, to identify patients with drug-resistant hypertension, is a rational first step to increase the a priori chance of renal artery stenosis. Amlodipine- or enalapril-based regimens are equally effective for this purpose.

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group.

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.

Accuracy of normal-dose contrast-enhanced MR angiography in assessing renal artery stenosis and accessory renal arteries.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of breath-hold contrast-enhanced MR angiography in the assessment of renal artery stenosis and accessory renal arteries using a standard dose of gadolinium. SUBJECTS AND METHODS: Thirty-eight patients suspected of having renal artery stenosis underwent MR angiography and intraarterial digital subtraction angiography, which was the method of reference. Three-dimensional gradient-echo MR subtraction angiography (TR/TE, 5.8/1.8 msec) was performed on a 1.5-T imager using a phased array body coil. Before imaging, a separate timing bolus sequence was used, administering 1.0 ml of contrast agent. Gadopentetate dimeglumine (15 ml) was injected using an MR power injector. Two observers, who were unaware of each other's interpretation and of MR findings, assessed digital subtraction angiography. Likewise, two other observers assessed MR angiography. RESULTS: Digital subtraction angiography depicted 75 main and 17 accessory renal arteries (n = 92). All main renal arteries and 13 accessory renal arteries were identified on MR angiography. Compared with digital subtraction angiography, MR imaging correctly classified 57 of 66 arteries without a hemodynamically significant stenosis (0-49%), 22 of 22 arteries as significantly stenotic (50-99%), and four of four occluded arteries; five stenoses were overestimated. There was one false-positive finding of an accessory renal artery on MR angiography that was identified retrospectively on digital subtraction angiography. Interobserver agreement was high. Sensitivity and specificity for grading significant stenosis were 100% and 85%, respectively. CONCLUSION: Contrast-enhanced MR angiography, using +/-0.1 mmol/kg of gadolinium, is an accurate method in the assessment of renal artery stenosis and accessory renal arteries.

Intratumor heterogeneity of k-ras and p53 mutations among human colorectal adenomas containing early cancer.

The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k-ras oncogene and of the p53 oncosuppressor gene during the adenoma-carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity. The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k-ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p-value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k-ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p-value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01). Intratumor homogeneity of k-ras status during the human colorectal adenoma-carcinoma sequence suggests that the role of k-ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.

[Malignant hypertension in a young man with renal artery occlusion diagnosed with magnetic resonance angiography]. / Maligne hypertensie bij een jongeman met nierarterieafsluiting gediagnosticeerd met magnetische-resonantieangiografie.

A male aged 22 years developed a hypertensive crisis with encephalopathy after his antihypertensive medication had been discontinued with a view to extended diagnostics. Immediate intensive treatment led to rapid and complete recovery. By using gadopentetate acid enhanced magnetic resonance angiography it is possible to obtain a clear image of the morphology of the kidneys and the renal vasculature without the use of iodinated contrast media and arterial catheterisation. This technique revealed an occluded renal artery and a recent infarction that possibly had led to the serious and threatening events.