Influence of epidermal growth factor/transforming growth factor alpha and polyamines on Caco-2 cell proliferation.
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Caco-2 Cells↗
Biomedical subjects
W F Caspary
Publications and source records attributed to W F Caspary.
[Diagnosis of sprue/celiac disease].
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Autoantibodies↗
Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma.
In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.
Adolescent↗
Risk of gastrointestinal bleeding associated with Helicobacter pylori infection in patients with hemophilia or von Willebrand's syndrome.
BACKGROUND: Many episodes of bleeding in the upper gastrointestinal tract are caused by Helicobacter pylori infection. Because these episodes present a life-threatening complication in patients with bleeding disorders, we prospectively investigated the prevalence of H. pylori infection in patients with hemophilia A or B and with the von Willebrand syndrome. METHODS: Seventy patients (54 men, 16 women, ages 40 +/- 11 years) and 100 age-related volunteers (63 men, 37 women, ages 39 +/- 9 years) were tested for H. pylori infection using the 13C urea breath test. Fifty-four patients with hemophilia and 16 patients with von Willebrand syndrome participated. RESULTS: Thirty-three (33%) of the controls and 24 (34.3%) of the patients showed positive 13C urea breath tests (p = .97). Nineteen (35.2%) patients with hemophilia and 5 (31.3%) patients with von Willebrand syndrome were positive for H. pylori. History of dyspeptic symptoms (28% vs. 26%) were not different in patients and controls (p = .91). Gastric ulcers (20% vs. 5%) and duodenal ulcers (7% vs. 5%) were diagnosed more often in patients with bleeding disorders. Fourteen of the patients (20%), but none of the controls had a history of gastrointestinal bleeding (p < .001). CONCLUSIONS: The rate of H. pylori infection and dyspepsia in patients with bleeding disorders is similar to the prevalence in the normal population. Due to increased bleeding complications, H. pylori screening and therapy appears mandatory in patients with bleeding disorders.
Adult↗
[Ultrasound lymph node imaging in the abdomen and retroperitoneum of healthy probands].
PURPOSE: Transabdominal ultrasonography is able to detect normal sized perihepatic lymph nodes. The role of transabdominal ultrasonography in detecting normal lymph nodes in other abdominal locations has not yet been examined. METHODS: 92 healthy volunteers (57 male, 35 female; age: 33 +/- 9 [19-66] years) were examined by transabdominal ultrasonography. The peripancreatic region, the location between the inferior vena cava and aorta, left paraaortal region, and the right mesenteric region next to the terminal ileum were studied with high resolution ultrasound. All transabdominal ultrasound examinations were performed with a 3.5 and 5 MHz probe using a special magnification mode without substantial loss of resolution (RES-mode, Acuson) and additionally by colour doppler imaging (Acuson XP). RESULTS: In 80/92 (87%) of the healthy subjects, all regions could be adequately visualized. In 72% of patients with adequate visualization, abdominal lymph nodes were detectable. Abdominal lymph nodes could be sonographically detected peripancreatically in 14/80 (18%), in the location between the inferior vena cava and aorta in 44/80 (55%), in the left paraaortal region in 32/80 (40%), and in the right mesenteric region next to the terminal ileum in 31/80 (39%) of the healthy subjects. CONCLUSION: High resolution ultrasonography is able to detect normal lymph nodes in different abdominal locations in 72% of healthy subjects. Sonographic detection of singular normal-sized abdominal lymph nodes is not indicative of abdominal disease.
Abdomen↗
Is pancreatoscopy of any benefit in clarifying the diagnosis of pancreatic duct lesions?
BACKGROUND AND STUDY AIMS: Modern fine-caliber endoscopes enable clinicians to directly visualize the pancreatic duct. They allow intraductal manipulation under optical control. We tried to evaluate the additional diagnostic potential of pancreatoscopy in assessing inconclusive intraductal pancreatic changes. PATIENTS AND METHODS: We prospectively performed 20 pancreatoscopies in 18 patients with inconclusive ductal abnormalities that had been previously investigated by computed tomography (CT) scan, abdominal ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). The CHF-BP 30 (Olympus Optical Co., Japan) endoscope with an outer diameter of 3.1 mm and an instrumentation channel of 1.2 mm was used. Biopsies, cytological brushing and fluid collection were carried out, and the site of ductal abnormality was visualized. Endoscopic sphincterotomy (EST) was carried out in every patient prior to insertion of the pancreatoscope. RESULTS: Seven intraductal tumors were histologically confirmed, i.e. five intraductal papillary mucinous tumors and two adenocarcinomas. Benign appearance of the intraductal lesion plus negative histopathological examinations were confirmed by a follow-up of two years in eight patients. Five had chronic pancreatitis, and a further three had pancreatitis with strictures, blood clot obstruction, and idiopathic benign stricture, respectively. There were no complications with the exception of one bleeding episode after EST; no pancreatitis occurred. CONCLUSIONS: Pancreatoscopy is of diagnostic value in addition to CT, transabdominal ultrasound and ERCP in the differential diagnosis of poorly defined pancreatic lesions, particularly when assessing alterations of the ductal caliber without parenchymatous lesions.
Adenoma↗
Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction.
BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is not without risks, and is also ineffective in about half of patients with type III sphincter of Oddi dysfunction (SOD), i.e. those without clinical evidence of biliary obstruction (normal liver tests, normal bile duct diameter, and regular drainage time at endoscopic retrograde cholangiography). The present study therefore investigated the efficacy and safety of endoscopic botulinum toxin (BTX) injection into the papilla of Vater, and analyzed whether the symptomatic response to BTX injection might be a predictor of outcome for endoscopic sphincterotomy. PATIENTS AND METHODS: Twenty-two patients who had undergone cholecystectomy and had manometrically confirmed type III SOD were enrolled during a three-year study period. All patients received treatment with an endoscopic single-shot injection of 100 mouse units of BTX into the papilla of Vater. Initial symptomatic responses were analyzed six weeks later. If the BTX injection had been ineffective, or if biliary symptoms recurred after initial benefit during the follow-up period, endoscopic manometry and endoscopic sphincterotomy were performed. All patients then received further prospective clinical follow-up examinations. RESULTS: With the exception of one patient with mild pancreatitis (4.5%), no side effects were observed after endoscopic BTX injection. Six weeks after BTX injection, 12 SOD patients (55%) were symptom-free, but ten patients (45%) were not. However five of these ten SOD patients who did not experience symptomatic benefit from BTX injection had normal basal sphincter of Oddi pressures (< 40 mmHg) at this time, and none of these five patients was free of complaints after subsequent endoscopic sphincterotomy. Two of the remaining five patients with sustained sphincter hypertension after BTX injection benefitted from endoscopic sphincterotomy. Eleven of the 12 SOD patients who had initially responded to BTX injection developed recurrent symptoms after a median period of six months. Manometry revealed sphincter hypertension in all 11 cases, and all patients became free of complaints again after endoscopic sphincterotomy during a median follow-up of a further 15 months. Overall, 11 of the 12 patients who responded to BTX injection, versus two of the ten patients who did not gain pain relief after BTX injection, later benefitted from endoscopic sphincterotomy (p < 0.01). CONCLUSIONS: Endoscopic injection of botulinum toxin into the papilla of Vater is a safe procedure and provides short-term relief of symptoms in half of patients with type III SOD. Our results also indicate that the clinical response to BTX injection can predict whether SOD patients will gain long-term benefit from endoscopic sphincterotomy.
Adult↗
Polyamine uptake across the basolateral membrane of the enterocyte is mediated by a high-affinity carrier: a study using isolated basolateral membrane vesicles.
BACKGROUND/AIMS: Polyamine uptake from the circulation plays an important role in the maintenance of the intracellular polyamine content during extensive proliferation in intestinal mucosal cells. METHODS: Isolated basolateral membrane vesicles of the rabbit enterocyte were used to characterize polyamine transport across the basolateral side of the intestinal epithelium. Incorporation of spermidine and spermine into the basolateral membrane was rapid, although 30-60% of polyamines were initially bound to the basolateral membrane. In order to avoid the influence of binding on the actual uptake into the vesicles, polyamine incorporation was measured at 37 and 4 degrees C, and kinetic parameters were calculated from the difference in polyamine incorporation rates at these temperatures. RESULTS: Uptake kinetics was saturable, with Km values of 13.34 and 12.35 micromol/l and Vmax of 159 and 105 pmol/mg protein/ min for spermidine and spermine, respectively. It was also temperature dependent, with Q10 values (calculated between uptake velocities at 37 and 25 degrees C) of 2.56 for spermidine and 1.90 for spermine. At physiological pH, polyamine uptake was at its highest. Since at this pH polyamines are fully charged, charge might be essential for polyamines to be taken up across the basolateral membrane. Polyamine uptake was inhibited by di-, tri- and tetracations, and there was no evidence for sodium cotransport. Transport of putrescine was not inhibited by spermine and spermidine, although spermidine inhibited spermine uptake in a competitive manner, with Ki of 127 micromol/l. CONCLUSION: These results imply that a saturable high-affinity transport system for polyamine does exist at the basolateral side of the enterocyte. Such a transport system may be responsible for the active transport of polyamine into rapidly proliferating enterocytes.
Animals↗
Hepatic and portal vein flow pattern in correlation with intrahepatic fat deposition and liver histology in patients with chronic hepatitis C.
OBJECTIVE: The flow pattern in hepatic veins depends on cardiac physiology and liver histology. The aim of our study was to determine the dependence of the flow pattern of hepatic and portal veins in relation to histologic features in patients with chronic hepatitis C. SUBJECTS AND METHODS: In 135 patients with chronic hepatitis C, the Doppler sonography spectrum of the right hepatic vein was classified as triphasic, biphasic, or monophasic. The flow of the portal vein was characterized according to the undulation (velocity(max,min)). A liver biopsy was performed during sonography, and biopsy specimens were semiquantitatively evaluated on a histologic activity index and a score of the hepatic fat content. Multiple logistic regression analysis was used to identify the histologic features that might contribute to the type of flow pattern. RESULTS: The hepatocyte fat content was the only variable associated with an independent effect on the type of flow pattern (monophasic versus triphasic; odds ratio, 16.26; 95% confidence interval, 6.38-41.45; p < .0001). A pronounced undulation in the portal vein was associated with portal inflammation but not with other parameters of the histologic activity index or the intrahepatic fat deposition. CONCLUSION: On sonography, the normal flow pattern in the right hepatic vein is triphasic. The monophasic flow pattern in the right hepatic vein is mainly caused by intrahepatic fat deposition and occasionally by inflammatory or fibrotic changes. Conversely, the flow pattern of the portal vein is mainly influenced by portal inflammation.
Adult↗
[Antibody diagnosis iin sprue/celiac disease].
The clinical appearance of celiac disease is diverse, often times uncharacteristic and may therefore be very difficult to diagnose. Furthermore, severe inflammation of the small bowel can be present without gastrointestinal symptoms. It is estimated that most subjects with celiac disease are not diagnosed. Yet, early diagnose is desirable, since celiac disease causes growth retardation in untreated children and is potentially cancer disposing. Thus, all patients should adhere to a strict gluten-free diet. The role of antibody testing and small bowel biopsy in celiac disease will be discussed. In the future, the development of new tests may allow screening of large populations.
Antibodies↗
[Structure and quality of German-language gastroscopy information forms from the patients' viewpoint].
UNLABELLED: Information about procedure and risks is prerequisite for obtaining informed consent for endoscopy. This prospective and randomized investigation evaluated (i) the extent of patients' information needs and (ii) the formal quality (language, ease of understanding, length, figures etc.) of three information forms concerning upper CI-endoscopy issued in 1995 by DIOmed (1), perimed compliance (2), and PERIMED-spitta (3) as judged by the patients. (iii) Outcome quality was investigated as the influence of these forms on understanding why and how endoscopy was performed as well as the influence on feeling threatened. Furthermore patients' anxiety was assessed by using Spielberger's state-trait anxiety inventory (STAI). 218 patients completed the investigation (n = 73; 70; 75, respectively). 60% claimed the need for a detailed explanation of the planned endoscopy and 48% said they wanted exhaustive informations about potential complications and risks. The three forms (length 819, 771, 1,245 words) were entirely read by 87%, 89% and 82% of the patients. Positive language, adequate length (69%, 69%, 71%) and adequate layout were evenly attributed to the three forms. A high impact of the figures for understanding was found more frequently (48%, 46%, 35%) with (1) and (2) and language war regarded easy by 57%, 54% and 44%, respectively. Flesh's reading ease score, however, proved a sophisticated niveau of language with all three forms. The indication for endoscopy (37%, 49%, 56%) and explanation of performance (43%, 43%, 63%) was superior with (3). This form also reduced anxiety as judged by STAI-means, overall STAI-changes, and relevant changes (> or = 5 points). Form (2) increased patients' anxiety. CONCLUSION: While the formal quality of all information forms is appreciated by patients both their reading ease score and figures should be improved. A significant reduction of anxiety can be achieved by appropriate selection of the information material.
Adult↗
S-adenosylmethionine decarboxylase activity and utilization of exogenous putrescine are enhanced in colon cancer cells stimulated to grow by EGF.
UNLABELLED: Polyamines spermidine and spermine and their precursor putrescine are necessary for cell growth. Polyamine content is high in rapidly growing malignant cells, due to enhanced putrescine synthesis by ornithine decarboxylase (ODC), and increased uptake. In contrast to other cells of the body, colon cancer cells are exposed to high putrescine concentrations from the lumen. AIMS: To investigate the utilization of luminal putrescine in colon cancer, we studied the effect of a potent mitogen, epidermal growth factor (EGF), on the activity of the enzyme responsible for putrescine conversion, S-adenosylmethionine decarboxylase (SAMDC), in Caco-2 cells. METHODS: Cell counts, ODC and SAMDC activities and intracellular polyamines were evaluated in the presence and absence of exogenous putrescine in concentrations resembling those normally present in the colonic lumen. RESULTS: ODC and SAMDC activity and putrescine uptake were strongly stimulated by EGF. Both synthesized and absorbed putrescine was rapidly converted to spermidine and spermine after EGF. Conversion pattern was identical in the cells stimulated with EGF only and EGF plus exogenous putrescine, indicating that, if stimulated to proliferate, colon cancer cells utilize the entire available putrescine pool. SAMDC inhibitor, methylglyoxal-bis-guanylhydrazone, induced growth arrest which was not reversed by exogenous putrescine, but only by high concentrations of spermidine. CONCLUSION: Enhanced proliferation in colon cancer cells is associated with increased SAMDC activity and rapid conversion of putrescine to spermidine and spermine. SAMDC might be a preferable target for therapeutic attempts to impair growth by reducing intracellular polyamine pools in colon cancer.
Adenosylmethionine Decarboxylase↗
[Sonographic detection of lymph nodes in the hepatoduodenal ligament].
BACKGROUND AND OBJECTIVE: In patients with chronic inflammatory liver disease modern methods of ultrasound can visualize enlarged lymph nodes in the porta hepatis. Number, size and total volume of lymph nodes in the hepatoduodenal ligament in healthy subjects and in patients with chronic viral hepatitis without cirrhotic changes were investigated. PATIENTS AND METHODS: Sonographic localization of the perihepatic lymph nodes was validated at post-mortem and intraoperatively. Following this, 92 healthy persons (57 men, 35 women; average age 33 +/- 9 years) and 48 patients (30 men, 18 women; average age 35 +/- 8 years) with serologically and histologically confirmed chronic viral hepatitis (30 with hepatitis C, 18 with hepatitis B) were investigated by abdominal ultrasound (Acuson 128, 3.5 and 5 MHz). The hepatoduodenal ligament was assessed according to a standardized procedure with demonstration of the lymph node positions ventral to the portal vein and between the portal vein and the inferior vena cava. RESULTS: Satisfactory imaging of the hepatoduodenal ligament was achieved in 83 of the 92 healthy persons (90.2%) and in 44 of the 48 patients with chronic viral hepatitis (91.7%). Lymph nodes were demonstrated in 60 of the 83 healthy subjects (72.3%) and in 43 of 44 patients with chronic hepatitis (97.7%). The mean perihepatic lymph node volume was 2.8 +/- 2.6 cm3 (0-9.7 cm3) and was thus significantly smaller (P = 10(-9)) than in the patients with chronic viral hepatitis (19.8 +/- 15.7 cm3 [0-62.4 cm3]). There was no significant difference in lymph node volume between patients with hepatitis B and those with hepatitis C (23.1 +/- 14.9 cm3 vs 18.9 +/- 15.6 cm3; P = 0.16). CONCLUSIONS: With adequate ultrasound technique enlarged lymph nodes can be demonstrated in the porta hepatis of almost all patients with chronic hepatitis B or C. Lymph nodes of normal size can often be imaged also in healthy persons if their localization is known. The demonstration of lymph nodes in the hepatoduodenal ligament in the area of the porta hepatis and the determination of their volume can be helpful in the diagnosis of chronic inflammatory liver disease.
Adult↗
[Risk factors in endoscopic manometry for suspected dysfunction of Oddi's sphincter].
OBJECTIVE: An increased incidence of pancreatitis having been reported after endoscopic manometry (EM) of the sphincter of Oddi, its incidence and severity as well as potential risk factors were investigated prospectively. PATIENTS AND METHODS: Between June 1988 and June 1996, standardised manometry was performed in 207 patients with suspected biliary and 23 with suspected pancreatic sphincter of Oddi dysfunction (SOD). All patients had been observed in hospital for at least 24 hours before the test. The diagnostic criteria of post-manometric pancreatitis (PMP) were epigastric pain and a rise in the concentration of serum amylase to at least three times normal. Potential risk factors for PMP were elucidated by uni- and multivariate analysis. RESULTS: Pancreatitis occurred in 19 patients (9%) with suspected biliary and in 6 (26%) with suspected pancreatic SOD (P < 0.01), 17 of mild and 8 of moderate degree. There were no deaths and no lasting sequelae. Previous pancreatitis after endoscopic retrograde cholangiopancreatography and the presence of SOD were identified as patient-associated risk factors (P < 0.01 for each). Method-associated risk factors were duration of manometry of more than 5 min (P < 0.05) and manometry in the pancreatic duct system (P < 0.05). The risk of pancreatitis was reduced by simultaneous endoscopic sphincterotomy for SOD (P < 0.01). CONCLUSION: Specific and often avoidable risk factors for postmanometric pancreatitis were identified: technical procedure, pancreatitis, SOD. With short duration of manometry, avoiding of manometry in the pancreatic duct system and with patient's informed consent for simultaneous endoscopic sphincterotomy risk of pancreatitis may be lowered.
Adult↗
[Helicobacter pylori--talked about by both patients and physicians].
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Helicobacter Infections↗
Enlargement of perihepatic lymph nodes in relation to liver histology and viremia in patients with chronic hepatitis C.
Inflammatory processes in organs frequently lead to hyperplasia of regional lymph nodes. In the present study, we investigated whether lymph node enlargement within the hepatoduodenal ligament may reflect the inflammatory activity within the liver of patients chronically infected with the hepatitis C virus (HCV). In 114 patients with chronic hepatitis C and 49 healthy controls, the total lymph node volume within the hepatoduodenal ligament was prospectively investigated by ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the same occasion, and specimens were semiquantitatively evaluated by the histological activity index (HAI). Hepatitis C viremia was assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%) and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected in all patients with chronic hepatitis C and in 33 of 45 controls. The mean perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than in HCV-infected patients with mild to moderate inflammatory activity, severe inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4 mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P < 10(-6)). No correlation was found between the total lymph node volume within the hepatoduodenal ligament, HCV genotypes, and liver function test results. In conclusion, enlargement of perihepatic lymph nodes in patients with chronic hepatitis C is predictive for the presence of severe inflammatory activity. The mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown but appears to be related to viral replication within the liver and the immune-mediated inflammatory response of the host.
Adult↗
Endoscopy is not a risk factor for Helicobacter pylori infection--but medical practice is.
BACKGROUND: Previous studies have suggested an increased risk for Helicobacter pylori infection in physicians who perform UGI endoscopy because of exposure to potentially infectious gastric secretions. Therefore, the H. pylori infection status of the endoscopy staff was compared with the H. pylori prevalence of medical staff without endoscopy experience and control subjects who had no contact with patients. METHODS: The noninvasive 13C-urea breath test was performed in 2108 volunteers: 1460 physicians (mean age 44 +/- 12 years), 235 nurses (33 +/- 10 years), and 413 control subjects (43 +/- 12 years) who were not working in clinical medicine. All subjects completed a questionnaire concerning the weekly frequency of gastroscopies and the duration of endoscopic experience. RESULTS: Overall, 37.4% of the physicians and 35.3% of the nurses, but only 27.1% of the control subjects were infected. H. pylori infection was not significantly different between endoscopy-performing (37.8%; n = 1091) and general medical staff (35.9%; n = 604). Neither the frequency of gastroscopies nor the duration of endoscopy practice correlated with H. pylori status. With respect to the age distribution; however, a statistically significant higher prevalence of H. pylori was observed in physicians and nurses compared with the 413 control subjects without patient contact (p < 0.01). CONCLUSION: UGI endoscopy is not a risk factor for H. pylori infection, but medical practice slightly raises H. pylori acquisition.
Adult↗