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Biomedical subjects

G Otto

Publications and source records attributed to G Otto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study.

BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Adult↗
PubMed2001

[Latex allergy. Perioperative management in anesthesia and cardiac anesthesia].

The frequency of perioperative allergic responses to latex has markedly increased over the last 10 years. High risk groups to develop sensitivity to latex include healthcare workers, workers in the latex industry, children suffering from congenital malformations such as spina bifida or urogenital deformities and patients who have undergone multiple surgical procedures. During surgery, patients have contact to a variety of products containing latex. To prevent anaphylactic reactions, all hospitals have to develop strategies to identify and manage patients sensitised to latex or belonging to high risk groups. The aim of this paper is to describe safe perioperative management in a latex-free environment.

Anesthesia↗
PubMed2001

Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma.

Experimental data have shown p53-dependent CD95 induction to be associated with increased levels of apoptosis after cytostatic treatment in hepatoma cells. A study of Japanese hepatocellular carcinoma (HCC) has reported an inverse correlation between CD95 and p53 expression. To examine the interaction of p53 and CD95 in tumors we investigated which alterations in p53 can be linked to loss of CD95 expression in European HCC. In 39 tumors we analyzed CD95 by immunohistochemistry and assessed the correlation between the findings of the p53 status as determined by immunohistochemistry and single-strand conformation polymorphism with polymerase chain reaction sequencing. In 10 of 14 tumors with evidence of p53 aberration there was also loss of CD95 expression, compared to 6 of 25 samples with apparent wild-type p53 (P<0.01). Three tumors with p53 mutations but sustained CD95 expression showed single base substitutions mapping to a narrow region of 20 codons in p53. A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. This is the first study to link loss of CD95 expression to specific p53 alterations in HCC. Functional p53 appears to be a major factor for CD95 expression in hepatocytes, the loss of which could contribute to chemoresistance and possibly immune evasion in hepatocellular carcinoma. Sustained CD95 expression in tumors with certain p53 aberrations may indicate functional heterogeneity of p53 mutants.

Adolescent↗
PubMed2001

Incidence of pressure ulcers in a neurologic intensive care unit.

OBJECTIVES: To determine the risk factors for pressure ulceration in an intensive care setting, to evaluate the Braden scale as a predictor of pressure ulcer risk in critically ill patients, and to determine whether pressure ulcers are likely to occur early in the hospital stay. DESIGN: Cohort study of patients with no preexisting ulcers with a 3-month enrollment period. SETTING: The neurologic intensive care unit and the neurologic intermediate unit at a primary care/referral hospital with a level I trauma center. PATIENTS: A total of 186 patients entered the study. INTERVENTION: Within 12 hrs of admittance, initial assessment, photographs, and Braden score were completed. Patients were re-examined every 4 days or at discharge from the unit, whichever came first. MAIN OUTCOME MEASURES: Determining risk factors for pressure ulcers, performing detailed statistical analyses, and testing the usefulness of the Braden score as a predictor of pressure ulcer risk. RESULTS: Twenty-three of 186 patients developed at least one pressure ulcer (incidence = 12.4%) after an average stay of 6.4 days. The Braden scale, which measures six characteristics of skin condition and patient status, proved to be a primary predictor of ulcer development. No ulcers developed in the 69 patients whose Braden score was 16 or higher. The likelihood of developing a pressure sore was predicted mathematically from the Braden score. However, being underweight was a significant and distinct factor in pressure ulcer development. CONCLUSIONS: Pressure ulcers may develop within the first week of hospitalization in the intensive care unit. Patients at risk have Braden scores of < or = 16 and are more likely to be underweight. These results suggest that aggressive preventive care should be focused on those patients with Braden scores of < or = 13 and/or a low body mass index at admission.

Adult↗
PubMed2001

Vacuolating cytotoxin of Helicobacter pylori plays a role during colonization in a mouse model of infection.

Helicobacter pylori, the causative agent of gastritis and ulcer disease in humans, secretes a toxin called VacA (vacuolating cytotoxin) into culture supernatants. VacA was initially characterized and purified on the basis of its ability to induce the formation of intracellular vacuoles in tissue culture cells. H. pylori strains possessing different alleles of vacA differ in their ability to express active toxin. Those strains expressing higher toxin levels are correlated with more severe gastric disease. However, the specific role(s) played by VacA during the course of infection and disease is not clear. We have used a mouse model of H. pylori infection to begin to address this role. A null mutation of vacA compromises H. pylori in its ability to initially establish infection. If an infection by a vacA mutant is established, the bacterial load and degree of inflammation are similar to those associated with an isogenic wild-type strain. Thus, in this infection model, vacA plays a role in the initial colonization of the host, suggesting that strains of H. pylori expressing active alleles of vacA may be better adapted for host-to-host transmission.

Animals↗
PubMed2000

[Budd-Chiari syndrome--a rare manifestation of hereditary thrombophilia].

Budd-Chiari syndrome is a rare manifestation of hereditary or acquired thrombophilia. We saw a case of Budd-Chiari syndrome in a 30-year-old woman leading to initial diagnostic difficulties. She underwent surgical side-to-side shunt and 9 weeks later an almost normal liver could be demonstrated on computerized tomography. Budd-Chiari syndrome should be considered if the Chiari triad with abdominal pain, hepatomegaly and ascites occurs in a patient. If necessary, invasive diagnostic procedures (e.g. angiography) must be performed. Therapeutic options are anticoagulative therapy and porto-systemic shunt, either as a TIPS or a surgical shunt. If severe liver failure occurs or liver cirrhosis is present, orthotopic liver transplantation is an additional option which also cures hereditary thrombophilia.

Activated Protein C Resistance↗
PubMed2000

[Surgery and interventional techniques in biliary tract diseases. Combined procedure or concurrent procedure?].

Bile duct stones, benign lesions of the bile duct, and malignant stenoses are principal entities requiring an interdisciplinary approach to diagnosis and treatment. There are unequivocal indications for surgical and interventional approaches. In many situations sparse data do not allow for clear-cut recommendations, which leads to a competition of surgical and interventional modes of treatment. In cholecystocholedocholithiasis, therapeutic splitting--endoscopic stone extraction and laparoscopic cholecystectomy--is at present the preferred strategy. The laparoscopic approach, including common bile duct exploration, may prove advantageous in the future. Emergency situations caused by choledocholithiasis--purulent cholangitis and biliary pancreatitis--require interventional treatment. For bile duct injuries with biliary leakage and treatment of short strictures, transpapillary or transhepatic prostheses may be adequate. In extended strictures or bile duct defects, surgical repair is required. In malignant stenoses, surgical treatment provides the longest survival. If operability is excluded, an interventional approach offers substantial palliation. The results of the different forms of stents and prostheses are comparable.

Biliary Tract Diseases↗
PubMed2000

Overexpression of p53 protein is not directly related to hepatitis B x protein expression and is associated with neoplastic progression in hepatocellular carcinomas rather than hepatic preneoplasia.

p53 mutations and binding of p53 to hepatitis B virus (HBV) x protein (HBx) have been suggested as alternative mechanisms of development of hepatocellular carcinomas (HCCs) in man, both processes resulting in intracellular accumulation of the protein which is detectable by immunohistochemical approaches. We have examined p53 expression in 149 explanted human livers, including 39 cases infected with HBV and 35 bearing HCC. p53 was demonstrated immunohistochemically in 51% of HCC samples (18/35), localized mainly in fast growing poorly differentiated areas. Accumulation of mutant p53 was verified by immunoprecipitation in most of the positive HCC samples (14/15), implying occurrence of p53 mutations. No cells positive for p53 were found in 354 preneoplastic hepatocellular lesions examined. This indicates that p53 mutation is associated with progression, rather than early development, of HCC in the low-aflatoxin B(1)-exposed region. The intracellular distribution patterns of p53 and HBx were different, with the former within nuclei and the latter confined to cytoplasmic compartment. HBx did not coimmunoprecipitate with p53. These data indicate that p53-HBx binding is infrequent, if it really occurs, in HBV-infected human liver, and that it cannot be a common mechanism of HBV-associated hepatocarcinogenesis. In addition, p53 accumulation was also observed in some parenchymal and ductular (oval) cells in cirrhotic livers and, more frequently, in fulminant hepatitis, being independent of HBx expression, and seemingly associated with the damage and/or regeneration of liver parenchyma, perhaps merely reflecting a cellular stress response.

Carcinoma, Hepatocellular↗
PubMed2000

Effect of tauroursodeoxycholic acid on bile acid-induced apoptosis in primary human hepatocytes.

BACKGROUND/AIMS: The accumulation of endogenous bile acids contributes to hepatocellular damage during cholestatic liver disease. To evaluate the potential role of apoptotic cell death due to increased concentrations of bile acids, primary human hepatocytes were treated with hydrophobic and hydrophilic bile acids. Because the Fas receptor-ligand system may mediate apoptosis in human liver cells, the effect of toxic bile acids on hepatocellular Fas receptor expression was evaluated. MATERIALS AND METHODS: Primary human hepatocytes were incubated with 50 and 100 microM glycochenodeoxycholic acid (GCDCA) and co-incubated with equimolar concentrations of tauroursodeoxycholic acid (TUDCA). To evaluate cytolytic and apoptotic effects, morphological alterations, hepatocellular enzyme release, nuclear DNA fragmentation and hepatocellular Fas receptor expression were evaluated. RESULTS: Apoptotic cell death was significantly increased after exposure to 50 microM GCDCA. Bile acid-induced apoptosis was not accompanied by hepatocellular Fas receptor overexpression. Tauroursodeoxycholic acid reduced apoptosis, as indicated by a significant reduction of oligonucleosomal DNA cleavage. Fas receptor expression was not significantly affected by tauroursodeoxycholic acid. At higher concentrations, direct cytolytic cell destruction was observed. CONCLUSION: Primary human hepatocytes represent a suitable model to study bile acid-induced apoptotic cell death. In these hepatocytes, already low bile acid concentrations might induce apoptotic cell death, which is not triggered by hepatocellular Fas receptor overexpression. Apoptotic DNA fragmentation was significantly reduced by co-incubation with tauroursodeoxycholic acid. The reduction of bile acid-induced apoptosis by ursodeoxycholic acid and its conjugates may contribute to the beneficial effects of these hydrophilic bile acids used for medical treatment of several cholestatic liver diseases.

Apoptosis↗
PubMed2000

[Segmental anatomy of the liver in computed tomography: do we localize the lesion accurately?].

PURPOSE: To evaluate if Couinaud's model using the planes of the major veins is an adequate tool for the presurgical localization of focal liver lesions. METHODS: Biphasic helical CT scans were performed on patients evaluated for liver resection using an increased IV bolus of contrast medium (180 ml lopamidol) and 2 mm image reconstruction increments. During the first evaluation, all liver lesions were localized in the conventional way using the planes of the 3 major hepatic veins and the portal trunks as segmental boundaries. In a second review, all lesions were attributed to the nearest peripheral portal branches. The path and the segmental attribution of the portal branches were analysed. Evaluations were performed using an interactive cine mode as well as three-dimensional reconstructions. RESULTS: 20 of 126 (16%) liver lesions had a different segmental location if the individual anatomy of the peripheral portal branch was used instead of the conventional technique. These different locations were due to the path of the portal trunks or the path of the peripheral portal branches crossing the planes of the major hepatic veins. CONCLUSION: The segmental anatomy of the liver using the planes of hepatic veins and portal trunks according to Couinaud is not an accurate tool for the presurgical localization of liver lesions in many cases.

Carcinoma, Hepatocellular↗
PubMed1999

Expression of MUC1, Thomsen-Friedenreich antigen, Tn, sialosyl-Tn, and alpha2,6-linked sialic acid in hepatocellular carcinomas and preneoplastic hepatocellular lesions.

The expression of epithelial mucins and Thomsen-Friedenreich-related antigens in preneoplastic and neoplastic hepatocellular lesions was systematically investigated using an in situ immunohistochemical staining approach. MUC1, MUC2, TF, sialosyl-TF, Tn, sialosyl-Tn, alpha2,3-linked sialic acid, and alpha2,6-linked sialic acid were examined in normal and cirrhotic human liver and in human hepatocellular carcinomas (HCCs) and cholangiocarcinomas. Normal hepatocytes and preneoplastic foci of altered hepatocytes did not express MUC1, MUC2, TF, Tn, s-Tn, or alpha2,6-linked sialic acid. In contrast, HCCs showed positive reactions for MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid. MUC2 was absent in normal biliary epithelial cells, but present in cholangiocarcinomas. The staining of MUC1, or s-Tn and alpha2,6-linked sialic acid in human normal liver tissues and various liver diseases did not change after specific treatments such as periodate oxidation or saponification, indicating that their expression in HCC does not result from incomplete glycosylation or low O-acetylation, respectively. MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid may be useful as indicators of progression of HCC in tissue sections, and perhaps also as targets for diagnostic and therapeutic approaches in vivo.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

Interleukin-6 and disease severity in patients with bacteremic and nonbacteremic febrile urinary tract infection.

An interleukin-6 (IL-6) response was detected in 81 patients with febrile urinary tract infections (UTIs). Bacteremic patients (n=24) had higher serum IL-6 at inclusion and throughout the first 24 h (P<. 01) and higher urine IL-6 from 6 h after start of therapy (P<.01) than did nonbacteremic patients (n=57). The serum and urine IL-6 responses remained elevated longer in the bacteremic group. Patients with clinical signs of pyelonephritis had higher serum and urine IL-6 concentrations than did other patients in the study population (P=.058, P<.01, respectively). IL-6 high responders had higher temperatures (P<.05) and C-reactive protein levels (P<.05, P<.01) than did low responders. The results demonstrate that IL-6 responses accompany febrile UTIs regardless of bacteremia and that the response reflects disease severity. The results suggest that IL-6 produced in the urinary tract can trigger the systemic host response in the absence of bacteremia.

Acute-Phase Reaction↗
PubMed1999

CDKN2 mutation is infrequent in german hepatocellular carcinoma.

For hepatocellular carcinoma, only scarce and controversial data on CDKN2 alterations are available. A high rate of mutations in a Chinese study contrasts with a low rate found in Japanese tumors and a CDKN2 germline mutation in 4/26 Swiss tumors examined. We analyzed 23 hepatocellular carcinomas from German patients for homozygous deletions of CDKN2 by coamplification with the human tyrosine hydroxylase (TH) gene and for CDKN2 mutations by PCR-single strand conformation polymorphism analysis and direct DNA sequencing. Our results indicate the lack of homozygous deletions. In one tumor, DNA sequencing showed a GCG-ACG (alanine-threonine) substitution at codon 148, a polymorphism in exon 2 of CDKN2. We conclude that the alteration of CDKN2 by deletion or mutation appears not to be a frequent event in hepatocarcinogenesis in German patients.

Adolescent↗
PubMed1999

Effect of anesthesia on a whole blood lymphocyte proliferation assay in the rat.

Lymphocyte proliferation assays are commonly used to quantify the effects of immunosuppressive drugs in animal models, but the influence of anesthetic agents on those assays is not well understood. We used a whole blood proliferation assay to compare lymphocyte proliferation in blood drawn from normal male Lewis rats that were sedated using three common methods. Rats (n = 12) were serially bled from the orbital plexus while anesthetized with diethyl ether, methoxyflurane, or carbon dioxide. Before the beginning of the anesthetic trials, a random subset of the rats (n = 6) was bled via the jugular vein using only manual restraint to provide a baseline control group. A comparison of the lymphocyte proliferation results obtained under these four conditions (manual restraint, diethyl ether, methoxyflurane, or CO2) showed no significant differences. The only hematological variation seen was an elevation of the number of circulating lymphocytes when ether was used. We conclude that there is no justification for withholding sedation when bleeding rats for this type of lymphocyte proliferation. Furthermore, when considering the use of one of the agents examined in this study, the method can be chosen based on factors other than potential adverse effects on the assay results.

Anesthetics↗