Ron Winograd

Longitudinal monocyte human leukocyte antigen-DR expression is a prognostic marker in critically ill patients with decompensated liver cirrhosis.

Background: Critical illness in cirrhotic patients is associated with a poor prognosis and increased susceptibility to infections. Monocyte HLA‐DR expression is decreased in cirrhotic patients, but its prognostic value has not been investigated prospectively.

The interleukin‐6 (IL6)–174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6

Septic shock is associated with a high mortality and an excessive activation of immune cascades. Interleukin (IL)‐6 has been found to be a key cytokine in the pathogenesis of severe sepsis, but the importance of a regulatory polymorphism within the IL6 promoter has been controversial in these patients. The aim of the study was therefore to systematically investigate the IL6–174 G/C promoter genotype with regard to the presence of shock in patients with sepsis, the IL6 serum levels, and the ex vivo secretion of IL6, respectively. Overall, 112 consecutive subjects with severe sepsis and septic shock according to consensus criteria were enrolled. The ex vivo secretion of IL6 after stimulation with lipopolysaccharide (LPS) in a whole blood assay and the IL6 serum concentrations were determined after admission of the patients. Among the 112 subjects with severe sepsis, 85 patients fulfilled the criteria of septic shock. In these patients, the frequency of the mutated C‐allele of the IL6 promoter polymorphism was significantly (P = 0.04) higher compared to that in individuals without shock. IL6 serum concentrations were highest in patients with the GG genotype (mean 2209 pg mL−1), followed by CG genotype (mean 1113 pg mL−1), and lowest in individuals with the CC genotype (mean 256 pg mL−1). Interestingly, a significantly (P = 0.005) higher ex vivo secretion of IL6 is detected in heterozygote individuals (535 pg mL−1) and patients with the IL6 CC genotype (555 pg mL−1) compared to patients with the –174 GG genotype (276 pg mL−1). In conclusion, the IL6–174 G/C promoter genotype is associated with shock in patients with sepsis. Functionally, the mutated C‐allele is correlated with low IL6 serum concentrations, but a high ex vivo secretion after LPS stimulation. These results further indicate a complex regulation of the expression of IL6 during infection and have implications for the design of immune intervention trials.

Classification of Colon Polyps in NBI Endoscopy using Vascularization Features

The evolution of colon cancer starts with colon polyps. There are two different types of colon polyps, namely hyperplasias and adenomas. Hyperplasias are benign polyps which are known not to evolve into cancer and, therefore, do not need to be removed. By contrast, adenomas have a strong tendency to become malignant. Therefore, they have to be removed immediately via polypectomy. For this reason, a method to differentiate reliably adenomas from hyperplasias during a preventive medical endoscopy of the colon (colonoscopy) is highly desirable. A recent study has shown that it is possible to distinguish both types of polyps visually by means of their vascularization. Adenomas exhibit a large amount of blood vessel capillaries on their surface whereas hyperplasias show only few of them. In this paper, we show the feasibility of computer-based classification of colon polyps using vascularization features. The proposed classification algorithm consists of several steps: For the critical part of vessel segmentation, we implemented and compared two segmentation algorithms. After a skeletonization of the detected blood vessel candidates, we used the results as seed points for the Fast Marching algorithm which is used to segment the whole vessel lumen. Subsequently, features are computed from this segmentation which are then used to classify the polyps. In leave-one-out tests on our polyp database (56 polyps), we achieve a correct classification rate of approximately 90%.

Impedance characteristics of normal oesophageal motor function.

Objective To obtain detailed data about the correlation between oesophageal peristalsis and bolus transport for clinical oesophageal motility testing. Methods Oesophageal motility testing was performed in 25 healthy subjects by using the newly developed technique of concurrent impedancometry and manometry. Parameters of oesophageal motility and bolus transport as well as the correlation between transit and motility were analysed after swallowing saline or yogurt. Results Detailed data about bolus transport and oesophageal motility could be obtained during a single investigation step. Air was observed in front of the bolus in 76% of the swallows. Resting baseline impedance was significantly higher in the oesophagus than in the stomach (2832 ± 118 &OHgr; vs 688 ± 119 &OHgr;). The deglutitive impedance gradient was 222 ± 26 &OHgr; for saline and 482 ± 38 &OHgr; for yogurt. Bolus propagation velocity and bolus transit time as impedance parameters of bolus transport discriminated fluid from semisolid bolus (4.0 ± 0.1 cm/s vs 3.2 ± 0.1 cm/s and 9.9 ± 0.2 s vs 11.5 ± 0.2 s, for saline vs yogurt), while contraction wave amplitude as a manometry parameter of oesophageal motor function did not (91.4 ± 7.5 mmHg vs 80.7 ± 9.4 mmHg, for saline vs yogurt). There was a poor correlation between bolus propagation velocity and contraction wave amplitude. Conclusions Impedance parameters of normal oesophageal motor function have been characterized. Impedancometry and manometry provide different but complementary data about oesophageal motor function. Concurrent impedancometry and manometry allows detailed monitoring of oesophageal motility and bolus transit, which may open new perspectives for comprehensive oesophageal motility testing.

Characteristics of oesophageal bolus transport in patients with mild oesophagitis.

Objective Patients with gastroesophageal reflux disease (GORD) frequently have oesophageal motility disturbance. However, detailed data about bolus transport characteristics in these patients are still lacking. In the present study the new technology of concurrent impedance manometry was applied for characterization of oesophageal motor function in patients with mild GORD. Methods Oesophageal motility testing was performed in 25 patients with mild GORD (group 1) as compared to 25 healthy subjects (group 2) employing the technique of concurrent impedancometry and manometry. Oesophageal motility as well as patterns and parameters of bolus transport after the swallowing of saline or yogurt were analysed. Results According to manometry the velocity of the contraction wave was similar in both groups. Mid-distal contraction amplitude in group 1 was still in the normal range but significantly lower than in group 2 (57.4±4.5 mmHg vs 91.4±7.5 mmHg for saline, and 47±4.1 vs 80.7±9.4 mmHg for yogurt). According to impedance measurements, bolus transport was significantly slower (3.6±0.1 vs 4.0±0.1 cm/s for saline and 3.0±0.1 vs 3.2±0.1 cm/s for yogurt), and post-deglutitive impedance was significantly lower in group 1: 2110 Ω±116 Ω versus 2542 Ω±152 Ω (P<0.01) with saline and 1862 Ω±108 Ω versus 2348 Ω±148 Ω with yogurt (P<0.01). GORD patients showed several pathological bolus transport patterns, which were not observed in healthy subjects. Gastroesophageal liquid reflux was observed between the swallows. Conclusions In patients with mild GORD concurrent impedancometry and manometry is sufficiently sensitive for the detection of minor oesophageal dysmotility. Several pathological features have been characterized including delayed bolus transport, impaired propulsive volume clearance, pathological transport patterns and pathological reflux patterns.

Assessment of inflammatory and fibrotic stenoses in patients with Crohn's disease using contrast-enhanced ultrasound and computerized algorithm: a pilot study.

Purpose: The development of stenosis is a typical complication of Crohn’s disease and represents a serious diagnostic and therapeutic challenge. The aim of the present study was to define objective quantitative measures of stricture characteristics (fibrostenotic/cicartricial vs. inflammatory) using contrast-enhanced ultrasound (CEUS) in patients with stenotic Crohn’s disease. Materials and Methods: During a period of 18 months, 18 consecutive patients with Crohn’s disease and manifestation of a localized significant small bowel stenosis were prospectively recruited. Standardized ultrasound (US) examination, color-coded duplex sonography and CEUS using SonoVue® were performed. Quantitative measurements of bowel wall vascularity were determined using computerized algorithms (Bracco QONTRAST software). The quality of stenosis (fibrostenotic vs. inflammatory) was classified in a 4-point scale, and the diagnostic/prognostic power of the US and clinical tests upon initial presentation were compared. Results: We established a novel standardized CEUS procedure using computerized algorithms to quantitatively examine stenoses in Crohn’s disease. An inflammatory origin of stenosis correlated significantly with a high Crohn’s Disease Activity Index (CDAI) (p < 0.01), the length of stenosis (p < 0.01) as well as the Limberg score (p < 0.01). There was no correlation between the type of stenosis and quantitative results of CEUS. Conclusion: Although bowel wall vascularity can be quantitatively assessed in stenotic areas by CEUS, this analysis does not improve the diagnostic power for the objective determination of the quality of stenosis at a single measurement. Semiquantitative analysis of bowel wall vascularity, length of stenosis, and CDAI may help to discriminate the origin of small bowel stenosis in Crohn’s disease.

Computer-based classification of small colorectal polyps by using narrow-band imaging with optical magnification

BACKGROUND Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for the differentiation between neoplastic and non-neoplastic colorectal polyps. OBJECTIVE To develop a computer-based method for classification of colorectal polyps. DESIGN A prospective study. SETTING University hospital. PATIENTS A total of 214 patients with colorectal polyps who underwent a zoom NBI colonoscopy. INTERVENTIONS A total of 434 detected polyps 10 mm or smaller were imaged and subsequently removed for histological analysis. MAIN OUTCOME MEASUREMENTS Diagnostic performance in polyp classification by 2 experts, 2 nonexperts, and a computer-based algorithm. RESULTS The expert group and the computer-based algorithm achieved a comparable diagnostic performance (expert group: 93.4% sensitivity, 91.8% specificity, and 92.7% accuracy; computer-based algorithm: 95.0% sensitivity, 90.3% specificity, and 93.1% accuracy) and were both significantly superior to the nonexpert group (86.0% sensitivity, 87.8% specificity, and 86.8% accuracy) in terms of sensitivity, negative predictive value, and accuracy. Subgroup analysis of 255 polyps 5 mm or smaller revealed comparable results without significant differences in the overall analysis of all polyps. LIMITATIONS No fully automatic classification system. CONCLUSIONS The study demonstrates that computer-based classification of colon polyps can be achieved with high diagnostic performance.

Long-term survival after diagnosis of hepatic metastatic VIPoma: report of two cases with disparate courses and review of therapeutic options.

This report describes two patients withpancreatic cholera caused by vasoactive intestinalpolypeptide (VIP)-producing tumors, which originated inthe pancreas and showed metastases in both hepatic lobes at time of diagnosis. However, the two tumorsdisplayed remarkably disparate clinical courses. Due tothe protracted but progressive course over more than 10years, a multifaceted therapeutic approach was performed to control symptoms and to improvequality of life. The long-acting somatostatin analogoctreotide was the most effective treatment forrelieving symptoms and correcting fluid and electrolytes disturbances. The effects of complementarytreatments, including systemic chemotherapy andhyperselective chemoembolization, as well as concurrentapplication of octreotide and prednisolone or interferon with respect to clinical symptoms, VIP levels,and tumor growth are reviewed. Our experience, althoughsmall, emphasizes the need for an expert, well-planned,adaptive, and multidisciplinary approach in the care of these complex patients.

A Comparison of Blood Vessel Features and Local Binary Patterns for Colorectal Polyp Classification

Colorectal cancer is the third leading cause of cancer deaths in the United States of America for both women and men. By means of early detection, the five year survival rate can be up to 90%. Polyps can to be grouped into three different classes: hyperplastic, adenomatous, and carcinomatous polyps. Hyperplastic polyps are benign and are not likely to develop into cancer. Adenomas, on the other hand, are known to grow into cancer (adenoma-carcinoma sequence). Carcinomas are fully developed cancers and can be easily distinguished from adenomas and hyperplastic polyps. A recent narrow band imaging (NBI) study by Tischendorf et al. has shown that hyperplastic polyps and adenomas can be discriminated by their blood vessel structure. We designed a computer-aided system for the differentiation between hyperplastic and adenomatous polyps. Our development aim is to provide the medical practitioner with an additional objective interpretation of the available image data as well as a confidence measure for the classification. We propose classification features calculated on the basis of the extracted blood vessel structure. We use the combined length of the detected blood vessels, the average perimeter of the vessels and their average gray level value. We achieve a successful classification rate of more than 90% on 102 polyps from our polyp data base. The classification results based on these features are compared to the results of Local Binary Patterns (LBP). The results indicate that the implemented features are superior to LBP.

Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility.

Matrix metalloproteinases are proteolytic enzymes which play a major role in resorption of collagen and other components of the extracellular matrix. They are controlled by specific inhibitors, so‐called tissue inhibitors of metalloproteinases (TIMPs). The balance between matrix metalloproteinases and TIMPs seems to play a major role in controlling extracellular matrix homeostasis and cell migration. The influence of TIMP‐1 on migration behaviour was explored in human hepatoma cells transiently and stably transfected with mouse TIMP‐1, and incubated with biologically active TIMP‐1. Transfection and biosynthesis were verified by Northern blotting, Western blotting, metabolic labeling, and reverse zymography. Overexpression of and incubation with TIMP‐1 resulted in suppressed migration and seemed to enhance cell‐cell contact. Using gelatin zymography and Western blotting we measured a significant increase of matrix metalloproteinases‐2 and matrix metalloproteinases‐9 in cells transfected with TIMP‐1. This new phenomenon may be of important physiological significance in modulating TIMP and MMP expression. Our results indicate a functional involvement of TIMP‐1 in matrix homeostasis and some automatic control in matrix turnover. J. Cell. Biochem. 75:346–355, 1999.