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Alexander Crispin

Publications and source records attributed to Alexander Crispin.

9 recordsLinked to original sources
PubMed2006

Methylation of serum DNA is an independent prognostic marker in colorectal cancer.

PURPOSE: Aberrant CpG island hypermethylation is a feature of a subgroup of colorectal cancers, which can be detected in the serum of affected patients. This study was designed to identify methylation targets with prognostic significance in the serum of patients with colorectal cancer. EXPERIMENTAL DESIGN: In a gene evaluation set consisting of sera from 24 patients with local colorectal cancers, 14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF, and hMLH1 were identified as potential serum DNA methylation markers. These genes were further analyzed in a test set of sera of 104 patients with colorectal cancer. RESULTS: Methylation of HLTF, HPP1/TPEF, and hMLH1 was found to be significantly correlated with tumor size, and methylation of HLTF and HPP1/TPEF was significantly associated with metastatic disease and tumor stage. Moreover, methylation of HPP1/TPEF was also associated with serum carcinoembryonic antigen. The prognostic relevance of methylation of these genes was tested in pretherapeutic sera of 77 patients with known follow-up. Patients with methylation of HPP1/TPEF or HLTF were found to have unfavorable prognosis (P = 0.001 and 0.008). In contrast, serum methylation of hMLH1 was not associated with a higher risk of death. Multivariate analysis showed methylated HPP1 and/or HLTF serum DNA to be independently associated with poor outcome and a relative risk of death of 3.4 (95% confidence interval, 1.4-8.1; P = 0.007). CONCLUSIONS: These data show that the methylation status of specific genes in the serum of patients with colorectal cancer has the potential to become a pretherapeutic predictor of outcome.

Adult↗
PubMed2006

Predictive value of the CARD15 variant 1007fs for the diagnosis of intestinal stenoses and the need for surgery in Crohn's disease in clinical practice: results of a prospective study.

BACKGROUND AND AIM: The diagnostic and therapeutic relevance of CARD15 genotyping in Crohn's disease (CD) for daily clinical practice has not been investigated so far. We therefore analyzed whether CARD15 variants are independent predictive factors for small bowel stenosis in CD evaluated by magnetic resonance enteroclysis (MRE). On the basis of these findings, the potential implications for patient management were investigated. METHODS: Eighty CD patients with clinical symptoms suggestive of small bowel stenosis were included. All patients were genotyped for the CARD15 variants c.2104C > T (p.R702W), c.2722G > C (p.G908R), and c.3019_3020insC (p.Leu1007fsX1008) and examined by MRE of the small bowel. RESULTS: CARD15 variants were found in 40 (50%) patients. MRE identified 31 (38%) patients with small bowel stenoses. Twenty-five of the 40 (62%) patients with at least one CARD15 variant were diagnosed of intestinal stenosis by MRE (odds ratio [OR] = 9.44; confidence interval [CI] 3.21-27.77; P = 0.00028, Bonferroni corrected). Particularly, the presence of the 1007fs variant was associated with an increased risk of an intestinal stenosis (OR = 12.00, CI 3.47-41.54, P = 0.00042, Bonferroni corrected). Twenty-one of 31 (68%) patients with stenoses required surgical intervention, with 13 of these 21 (62%) patients carrying the 1007fs variant. CONCLUSION: In the largest prospective study analyzing the diagnostic value of CARD15 variants in CD patients performed so far, we identified the 1007fs variant as strong predictor for intestinal stenoses with need for surgery in CD patients. Genotyping could therefore be an important diagnostic tool in clinical practice for identifying high-risk patients with specific diagnostic and therapeutic needs. Moreover, MRE is an excellent technique for diagnosing small bowel stenoses.

Adolescent↗
PubMed2005

The role of Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and CARD15/NOD2 mutations in the susceptibility and phenotype of Crohn's disease.

BACKGROUND: We investigated the influence of 2 common Toll-like receptor 4 (TLR4) polymorphisms on susceptibility and disease characteristics of Crohn's disease (CD). METHODS: Genomic DNA from 204 patients with CD and 199 unrelated controls was analyzed for the presence of 2 single nucleotide polymorphisms in the TLR4 gene, resulting in the amino acid substitutions Asp299Gly and Thr399Ile. In addition, the carrier status for the 3 common CD-associated CARD15/NOD2 gene mutations, Arg702Trp, Gly908Arg, and 1007fs, was determined. The frequency of the different genotypes was compared, and a detailed genotype-phenotype correlation was performed. RESULTS: An almost 2-fold increase in the frequency of the TLR4 Asp299Gly phenotype was observed in patients with CD (14.2%) compared with healthy controls (7.5%, P = 0.038, odds ratio = 2.03). The prevalence of a stricturing phenotype was increased in patients heterozygous for 1 of the TLR4 polymorphisms studied (Asp299Gly, 34.5%; Thr399Ile, 36.7%) compared with patients with wild-type TLR4 (17.1% and 16.7%; P = 0.04 and 0.02, respectively). The presence of the Asp299Gly polymorphism in the absence of CARD15/NOD2 mutations was a particularly strong predictor of the stricturing disease phenotype that was present in 47.4% of the patients with Asp299Gly+/NOD2- compared with 10.1% of the patients with the Asp299Gly-/NOD2+ status (P = 0.0009; P = 0.0004 for Thr399Ile+/NOD2- versus Thr399Ile-/NOD2+). In contrast, there was a trend toward a higher prevalence of the penetrating phenotype in the TLR4-/NOD2+ group (71.6%) compared with the TLR4+/NOD2- group (47.4%, P = 0.059). CONCLUSIONS: The TLR4 Asp299Gly polymorphism is a risk factor for CD. TLR4 and CARD15/NOD2 mutations may contribute to distinct disease phenotypes.

Adult↗
PubMed2004

CT measurement of coronary calcium mass: impact on global cardiac risk assessment.

Coronary calcium mass percentiles can be derived from electron beam CT as well as from multidetector-row CT of all manufacturers. Coronary calcium mass may serve as a more individualized substitute for age for cardiac risk stratification. The aim was to investigate the potential impact of CT coronary calcium mass quantification on cardiac risk stratification using an adjusted Framingham score. Standardized coronary calcium mass was determined by multidetector-row CT in a total of 1,473 patients (1,038 male, 435 female). The impact on risk stratification of replacing the traditional Framingham age point score by a point score based on calcium mass relative to age was tested. Any coronary calcium found in males in the age group of 20-34 years and females in the age group of 20-59 years results in an increase of the Framingham score by 9 and 4-7 points, respectively. Only in males 65 years of age and older, none or minimal amounts of coronary calcium decrease the Framingham score by three points. The coronary calcium mass and age-related scoring system may have impact on the reassignment of patients with an intermediate Framingham risk to a lower or higher risk group.

Adult↗
PubMed2004

The effect of clothes on sphygmomanometric and oscillometric blood pressure measurement.

AIM: We determined the effect of wearing clothes under the manometer's cuff on blood pressure in manual auscultatory sphygmomanometric and automatic oscillometric blood pressure measurement. METHODS: Two hundred and one subjects were examined with the auscultatory sphygmomanometric and the automatic oscillometric method, each with and without sleeved arm in random order. The auscultatory readings were blinded for the subjects' state of clothing. Common shirts and sweaters (thinner than 2 mm) were used. RESULTS: Based on confidence intervals of the differences between sleeved and non-sleeved arm measurements and equivalence test, sleeves did not lead to statistically significant effects. Measurements with and without sleeve can be accepted equal within an a priori defined interval of equivalence of +/-4 mmHg. DISCUSSION: This study shows that measuring blood pressure with the manometer's cuff over the subject's sleeve does not differ significantly from non-sleeved arm measurements. This is true for a sample that includes normotensive as well as hypertensive persons with a wide age range. For clinical practice, the not significant mean differences of 0.5-1.1 mmHg are interpreted as not relevant. In this study with a statistical power to find a difference of 4 mmHg, blood pressure measurements were found to be equivalent with and without clothes thinner than 2 mm.

Adult↗
PubMed2003

Ex vivo coronary atherosclerotic plaque characterization with multi-detector-row CT.

Multi-detector-row CT angiography (CTA) is a new technology that allows for non-invasive investigation of coronary atherosclerosis in patients. The relation between the morphology of atherosclerotic plaques assessed by CTA and histopathology is unknown. We investigated 11 human cadaver heart specimens. A mixture of methylcellulose and CT contrast media was injected into the coronary arteries to achieve in-vivo-like contrast enhancement within the coronary artery lumen. The morphologic pattern of atherosclerotic lesions found on CTA images and the tissue attenuation of non-calcified plaques were determined. After CTA imaging, atherosclerotic lesions in the coronary arteries were macroscopically identified and characterized histopathologically according to American Heart Association criteria. A total of 50 and 40 lesions were found macroscopically and by CTA, respectively. Thirty-three lesions could have been compared directly. The sensitivity of CTA compared with macroscopic detection of atheromas, fibroatheromas, fibrocalcified, and calcified lesions was 73, 70, 86, and 100%, respectively. The mean CT attenuation of predominantly lipid-rich and fibrous-rich plaques was significantly different (47+/-9 and 104+/-28 HU, respectively; p<0.01). Atherosclerotic coronary plaques detected by CTA may represent different stages of coronary atherosclerosis. The tissue attenuation of non-calcified plaques may allow for assessment of their predominant component.

Adult↗
PubMed2003

Detection and prognostic value of cytokeratin positive tumor cells in bone marrow of patients with renal cell carcinoma.

PURPOSE: Several investigations indicate the prognostic value of disseminated cytokeratin positive tumor cells in bone marrow of patients with carcinoma of different origin. In this study we evaluated the prognostic significance of epithelial cells in bone marrow of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Aspiration of bone marrow was performed preoperatively in 335 patients with RCC between 1990 and 1998. A total of 287 patients fulfilled all study inclusion (eg M0 R0 tumor stage) and exclusion (eg second malignancy during followup) criteria for the final analysis. Cytospin preparations were made after density gradient centrifugation of bone marrow samples and incubated with monoclonal antibodies directed against cytokeratin 18 (CK2) and pan-cytokeratin. Staining was performed using the alkaline phosphatase-anti-alkaline phosphatase method and 256 samples were evaluated. RESULTS In 25% (63 of 256) of the patients cytokeratin positive (CK+) cells were detected in bone marrow. Tumor progression (defined as tumor associated death, local recurrence or new metastases) was present in 12% (31 of 256) during the followup period (median 40 months), and 14% (9 of 63) with CK+ cells and 11% (22 of 193) with negative bone marrow status exhibited tumor progression. Survival analysis (log-rank test) showed no significant difference between the CK+ and cytokeratin negative group. The detection of CK+ cells was not an independent prognostic parameter in multivariate analysis (Cox regression model). CONCLUSIONS: These results indicate that the immunocytochemical detection of disseminated cytokeratin positive tumor cells in the bone marrow of patients with RCC has no prognostic significance.

Adult↗
PubMed2002

Subsegmental pulmonary emboli: improved detection with thin-collimation multi-detector row spiral CT.

PURPOSE: To compare different reconstruction thicknesses of thin-collimation multi-detector row spiral computed tomographic (CT) data sets of the chest for the detection of subsegmental pulmonary emboli. MATERIALS AND METHODS: A multi-detector row spiral CT protocol for the diagnosis of pulmonary embolism was used that consisted of scanning the entire chest with 1-mm collimation within one breath hold. In 17 patients with central pulmonary embolism, the raw data were used to perform reconstructions with 1-mm, 2-mm, and 3-mm section thicknesses. For each set of images, each subsegmental artery was independently graded by three radiologists as open, containing emboli, or indeterminate. RESULTS: For the rate of detection of emboli in subsegmental pulmonary arteries, use of the 1-mm section width yielded an average increase of 40% when compared with the use of 3-mm-thick sections (P <.001) and of 14% when compared with the use of 2-mm-thick sections (P =.001). With the use of 1-mm sections versus 3-mm sections, the number of indeterminate cases decreased by 70% (P =.001). Interrater agreement was substantially better with the use of 1-mm and 2-mm sections than with the use of 3-mm sections. CONCLUSION: For the diagnosis of subsegmental pulmonary emboli at multi-detector row CT, the use of 1-mm section widths results in substantially higher detection rates and greater agreement between different readers than the use of thicker sections.

Adult↗