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Biomedical subjects

G Judmaier

Publications and source records attributed to G Judmaier.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects.

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid.

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.

Acute-Phase Proteins↗
PubMed1993

Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease.

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.

Adult↗
PubMed1993

A combined biopsy-plugging device based on the Menghini- or Trucut needle for percutaneous liver biopsy: clinical experience.

Impaired blood clotting precludes percutaneous liver biopsy for histologic examination of liver tissue. The transjugular or laparoscopic approach are ways to reduce the risk of bleeding. These techniques, however, are laborious and confined to specialized centers. Methods of plugging the needle track with sealant presented so far are hampered by the need to leave either the cannula in situ or the need for a second percutaneous approach for the application of the sealant. We have tested a combined plugging-biopsy device allowing to perform the biopsy as a one-step procedure in patients with impaired clotting under laparoscopic vision control. In 37 patients either a modified Trucut or Menghini needle was tested. Handling of the Trucut needle proved easier. Tissue yield was satisfactory with both needles. Only one episode of bleeding was observed with a prototype Menghini needle. We conclude, that the combined plugging-biopsy device is a safe and reliable tool for obtaining liver tissue in patients with impaired blood coagulation.

Biopsy, Needle↗
PubMed1993

The role of neopterin in assessing disease activity in Crohn's disease: classification and regression trees.

Neopterin, a product of human monocytes/macrophages stimulated by gamma-interferon, was previously found to be correlated with clinical activity of Crohn's disease. The present investigation attempted to identify more precisely the role of neopterin for assessment of clinical activity in a multivariate setting. A broad panel of clinical and laboratory variables was obtained on 76 patients. Neopterin was determined in urine by high performance liquid chromatography. Using a 4-point clinical activity score as dependent variable, multivariate linear discriminant analyses were performed in order to identify subsets of statistically independent laboratory activity indices. Neopterin was shown to be an independent indicator for clinical activity. The significant variables were then tested together with the eight constituent variables of the Crohn's Disease Activity Index. The resulting model, which consisted of the three laboratory variables--erythrocyte sedimentation rate, serum protein and neopterin, together with pain score--was further subjected to two multivariate techniques for comparison: polychotomous logistic regression analysis and the technique of classification and regression trees. By all methods, neopterin was included into the multivariate models, confirming that its determination aids in the assessment of clinical activity in Crohn's disease.

Adult↗
PubMed1992

High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease.

OBJECTIVE: To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients. DESIGN: Cross-sectional study. SETTING: A referral-based university hospital. PATIENTS: Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease. MEASUREMENTS: The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history. RESULTS: Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics. CONCLUSIONS: Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.

Adolescent↗
PubMed1992

Critical study of consensus analysis.

Consensus analysis has been proposed as a statistical method by which the efficacy of clinical and laboratory tests of inflammatory activity can be assessed. This technique is claimed to overcome the need for an external "gold standard" as a reference method; instead, the consensus of all tests is used as the gold standard. We have evaluated the reliability of consensus analysis using data collected from patients with Crohn's disease. Our results demonstrate that the technique depends strongly on the correlation structure underlying the set of measures of disease used for analysis. This observation was supported by a series of conventional cluster analyses of the same set of variables. Furthermore, slight modifications of the algorithm had profound effects on the final result. We conclude that for the evaluation of tests of inflammatory activity, an external reference method, albeit an imperfect one, remains indispensable.

Clinical Laboratory Techniques↗
PubMed1992

Serum levels of cytokines in chronic liver diseases.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Adolescent↗
PubMed1992

[Wilson's disease with primary CNS manifestation--current status in diagnosis and therapy].

Five cases studied at our clinic are discussed and the literature reviewed with the aim of assessing the diagnostic value of various examination methods used for Wilson's disease and a modified diagnostic approach is suggested. CT and MRI are compared with regard to sensitivity, specificity and prognostic value. Almost regularly, MRI showed bilateral lesions in the basal ganglia in combination with structural changes in the brain stem. A pattern consisting of symmetrical lesions of the red nuclei, the periaqueductal grey region and, facultatively, the substantia nigra and the dentate nuclei was discovered and appeared almost pathognomonic. Follow-up studies revealed excellent reversibility of MRI changes by both penicillamine and trientine. Auditory evoked potentials showed the highest sensitivity and the best correlation with structural findings. Kayser-Fleischer corneal rings--a diagnostic requirement in the literature--were not found in all patients. The current state of therapy and therapy management is discussed on the basis of pathophysiological considerations. As possible complications of penicillamine administration the deterioration of the clinical condition after initiating therapy, and the risks associated with an abrupt termination of therapy are discussed in detail.

Adolescent↗
PubMed1992

[Prevention of the recurrence of duodenal ulcer with famotidine. Report of experiences with long-term therapy in an open clinical study].

In this open trial, 25 patients with identified duodenal ulcers were given long-term therapy of a single evening dose of 20 mg famotidine. 18 patients completed the study, 7 were withdrawn because of compliance difficulties. The patients included in this study had a long history of ulcer disease; ulcers were identified by endoscopy and they were healed after 4 or 8 weeks of H2-blocker therapy. Under long-term therapy with famotidine (Ulcusan), ulcers recurred in 3 patients after 3 months, a further 3 recurred after 6 months, and another 2 after 12 months. The recurrence of ulcers occurred in many patients without symptoms. Tolerance of the drug was good in all patients. No change in biochemical parameters was observed. Undesired side effects were not seen. Low dose famotidine therapy (20 mg Ulcusan tablets) is suitable in long-term treatment of peptic ulcer disease; frequent endoscopy would be advisable to detect recurrency of asymptomatically ulcers.

Adult↗
PubMed1991

Neural networks as a tool for utilizing laboratory information: comparison with linear discriminant analysis and with classification and regression trees.

Successful applications of neural network architecture have been described in various fields of science and technology. We have applied one such technique, error back-propagation, to a medical classification problem stemming from clinical chemistry, and we have compared the performance of two different neural networks with results obtained by conventional linear discriminant analysis or by the technique of classification and regression trees. The results obtained by the various models were tested for robustness by jackknife validation ("leave n out" method). Compared with the two other techniques, neural networks show a unique ability to detect features hidden in the input data which are not explicitly formulated as input. Thus, neural network techniques appear promising in the field of clinical chemistry, and their application, particularly in situations with complex data structures, should be investigated with more emphasis.

Alanine Transaminase↗
PubMed1991

Recombinant tumour necrosis factor alpha administered subcutaneously or intramuscularly for treatment of advanced malignant disease: a phase I trial.

The pharmacokinetics, toxicity and biological effects of subcutaneous and intramuscular treatment of cancer patients with recombinant tumour necrosis factor alpha (rTNF-alpha) was investigated. 17 patients suffering from refractory malignant disease were treated with either 1.0 micrograms/m2, 10 micrograms/m2 or 100 micrograms/m2 rTNF-alpha. Vital signs, peripheral blood cell counts, TNF and interferon (IFN) gamma serum levels, neopterin, beta 2-microglobulin, C reactive protein (CRP) and cortisol levels were measured immediately before and 2, 12, 24, 48 and 168 h after the first administration of rTNF-alpha. Tumour response was evaluated after 4 and 12 weeks of treatment. The pharmacokinetics followed the same characteristics as those reported for other cytokines. Major toxicities were dose dependent and comprised fever, constitutional symptoms and hypotension. TNF dependent changes were observed in serum levels of IFN-alpha, CRP, neopterin, beta 2-microglobulin, cortisol and white blood cell counts. No objective tumour response was observed. This study indicated that rTNF-alpha administered subcutaneously or intramuscularly results in measurable TNF serum levels, significant toxicity and biological response in absence of clinical efficacy in patients with advanced cancer.

Adult↗
PubMed1990

One-year treatment of chronic non-A, non-B hepatitis with interferon alfa-2b.

Thirty patients with chronic non-A, non-B hepatitis (24 male, six female; median age 38 years, range: 15-68 years) were treated with recombinant interferon alfa-2b for 1 year. Treatment was started with 5 million units interferon alfa-2b daily for 2 weeks followed by 2 million units daily for another 2 weeks. Further doses were titrated according to alanine aminotransferase values. After 1 year, treatment was stopped and a follow-up biopsy was obtained. Thereafter, patients were followed for 6 months. Of the 24 patients who completed the 1-year treatment period, 14 (58%) had normal alanine aminotransferase values at the end of the study, eight of whom showed transient increases while on treatment. In another seven (29%), alanine aminotransferase levels decreased by more than 50% of pre-treatment values but remained above the normal range. Biopsies at the end of treatment showed a complete disappearance of inflammatory activity in four and a marked improvement in eleven other patients. The results of this study indicate that a 1-year treatment with recombinant interferon alfa-2b of patients with non-A, non-B hepatitis was very effective at normalizing or improving serum transaminases and liver histology. However, the overall relapse rate was 57%, with relapse occurring in a greater proportion of patients with temporary breakthroughs during therapy (requiring dosage increase), and particularly of patients with only a partial response to treatment (serum transaminases decreased by greater than or equal to 50%). Thus, further studies are needed to establish the optimal dose and duration of treatment to induce a complete resolution of the disease.

Adult↗