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Biomedical subjects

W Tittor

Publications and source records attributed to W Tittor.

At least 19 recordsLinked to original sources
PubMed1997

Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years.

In recent retrospective studies, it was shown that subtypes of antimitochondrial antibodies (AMA) can help to discriminate between a benign [only anti-M9 and/or anti-M2 positive by enzyme-linked immunosorbent assay (ELISA)] and a rather progressive course (anti-M2, -M4 and/or -M8 positive). According to different constellations of these AMA subspecificities in ELISA and complement fixation test (CFT), four AMA profiles (A-D) were defined. In 1984 we started a prospective study based on 200 PBC patients with known AMA profiles in order to correlate the antibody pattern with the clinical outcome. Progression was defined primarily as the necessity of liver transplantation and death due to hepatic failure or variceal bleeding. At entry, 18 (9%) of the 200 patients had AMA profile A (only anti-M9), 57 (29%) profile B (only anti-M2 with or without anti-M9), 74 (37%) profile C (anti-M2 in association with anti-M4/-M8 by ELISA), and 51 (26%) profile D (anti-M2/-M4/-M8 by ELISA and CFT). At the beginning of the study, 177 patients had PBC stage I/II. During the observation period of ten years, ten patients died and in 18 orthotopic liver transplantation (OLT) was performed; all these patients belonged to profile C/D. Furthermore, 44% of the patients with profile C and 31% of the patients with profile D progressed to late stages, as defined by histology and clinical manifestations such as portal hypertension and increase of bilirubin, while only one of the patients with profile B and none of the profile A-patients developed late stage PBC. A significant increase of bilirubin was observed only in C/D-patients. AMA profiles did not change during the follow-up. In conclusion, AMA profiles discriminate between a benign and a progressive course of PBC already at early stages.

Adult↗
PubMed1996

Survival in alcoholic liver cirrhosis: prognostic value of portal pressure, size of esophageal varices and biochemical data. Comparison with Child classification.

A survival analysis was carried out based on the data of 190 male patients with alcoholic liver cirrhosis (Child A: 82.2%; Child B: 17.8%). Patients (mean age: 49.6 +/- 7.1 years) were examined during the period 1983-1990. Censoring in May 1993 was based on the recordings of the "Rentenversicherungsanstalten". There were no "drop-outs". During follow-up (mean: 4.2 years) 64 (33.7%) of the patients died. 13 potential prognostic variables were examined individually by drawing Kaplan-Meier curves and performing log-rank tests. Portal pressure, determined during hepatic vein catheterization as hepatic vein pressure gradient HVPG (P), size of esophageal varices, serum bilirubin, serum albumin, prothrombin time (Quick), thromboplastin time (PTT), cholinesterase (ChE) and Child scores were correlated to survival (p < 0.05), whereas age, gamma GT, IgA, drinking habits and additional diagnoses were not. A multivariate Cox regression analysis stepwise eliminated all but three variables: ChE, albumin and variceal size were included in the prognostic index PI of the final model. The usefulness of the model was tested by a cross validation method. No significant difference was found between estimated and observed survivorship functions. To compare the PI of the Cox model with Child's scores, ROC curves of sensitivity and specificity of predicting death within one, three and five years were constructed. Better prognostic efficiency was indicated for PI. Because ChE, albumin and the size of varices are determined as a routine in our clinic, we consider the construction of PI an advisable alternative to Child's classification.

Adult↗
PubMed1995

[Recurrent bleeding from colonic varices in portal hypertension. The successful prevention of recurrence by the implantation of a transjugular intrahepatic stent-shunt (TIPS)].

HISTORY AND CLINICAL FINDINGS: Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent bleeding from oesophageal varices. Half a year later he again was admitted to hospital because of recurrent passage of bloody stools. The cardiovascular status was stable; the liver was enlarged by 15 cm in the medioclavicular line. INVESTIGATIONS: Endoscopy revealed several varices in the colon near the right flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed portal hypertension with cirrhosis of the liver and partial thrombosis of the main trunk of the portal vein without any sign of cavernous transformation. TREATMENT AND COURSE: Because of the partial portal vein thrombosis it was decided to insert a transjugular intrahepatic portosystemic stent shunt. This obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%. With the shunt functioning well there were no further bleedings in the subsequent year. CONCLUSION: The only slightly invasive TIPS implantation is an effective therapeutic procedure for bleeding from colon varices caused by portal hypertension.

Colon↗
PubMed1992

[Diagnosis of alcohol-induced liver cirrhosis by indirect portal vein pressure measurement and liver venography].

Indirect measurement of portal pressure and hepatic venography using the balloon catheter technique were investigated to assess the stage of chronic alcoholic liver disease, especially, to diagnose cirrhoses. 80 patients were studied and were categorised in 4 groups according to their liver histology: normal liver (N, n = 6), fibrosis (F, n = 27), incomplete cirrhosis (F/C, n = 11), complete cirrhosis (C, n = 36). Medians of wedged hepatic venous pressure gradient P (= WHVP-FHVP) and of a semiquantitative venographic score S showed increasingly higher values with more severe stages of the disease. Portal pressure (P) and venographic appearance (S) were correlated significantly (r = 0.778, p less than 0.0001). P was most useful to diagnose cirrhosis: Precirrhotic forms were associated with pressure gradients P less than or equal to 5 mm Hg in 97%. Incomplete cirrhoses were distributed in about 50% above and below P = 5 mm Hg, for complete cirrhoses P greater than or equal to 8 mm Hg was found in 97%. Pressure gradients P greater than or equal to 5 mm Hg indicated cirrhotic disease with a specificity of 97%. Sensitivity for complete cirrhoses was also high (97%), for incomplete cirrhoses however low (47%). Venography and measurement of portal pressure as diagnostic tools to predict cirrhoses of alcoholic origin were clearly more useful than biochemical tests (serum bilirubin, quick and cholinesterase). In comparison to laparoscopy the acceptance by patients is higher and the risk is lower if patients with known adverse reactions to contrast materials and risk of thyreotoxicosis induced by iodine are excluded.

Adult↗
PubMed1991

Logistic-regression model for assessing portal hypertension by measuring hyaluronic acid (hyaluronan) and laminin in serum.

We earlier observed a positive correlation between portal venous pressure (PVP) and the concentration of laminin in serum. Here we investigated whether the diagnostic efficacy could be improved by considering additional analytes and application of multivariate statistical analysis. In 102 patients with fibrotic liver disease of various etiologies we measured PVP as the gradient of the wedged and free hepatic venous pressures and determined the concentrations of hyaluronic acid and laminin in serum. Regression coefficients established by logistic regression in this group were subsequently used to predict portal hypertension (PVP greater than mmHg) in an independent group of 45 patients. By comparison with the known PVP, we obtained a sensitivity of 0.83 (confidence interval: 0.63-0.93) and a specificity of 0.82 (0.61-0.93) for diagnosis of portal hypertension by means of the concentrations of hyaluronic acid and laminin in serum. Application of the model is suggested as a tool for pre-screening and monitoring patients to be subjected to assessment of portal hypertension.

Adult↗
PubMed1988

Evaluation of serum aminoterminal procollagen type III propeptide as an index of portal hypertension and esophageal varices in chronic liver diseases.

The concentration of the aminoterminal propeptide of type III procollagen (P-III-P) was determined in serum of cubital vein and hepatic vein of patients with various types of chronic liver diseases (n = 111) and correlated with the portal venous pressure and with the degree of esophageal varices. The P-III-P level in all chronic liver diseases was correlated (rS 0.542, p less than 0.001) with the portal venous pressure, but in liver fibrotic subjects (n = 29) this correlation (rS 0.310) was not significant, in liver cirrhosis (n = 30) the respective correlation was found to be weak (rS 0.333, p less than 0.05) and similar to that in patients with unspecified chronic liver diseases (n = 52) (rS 0.425, p less than 0.01). Sensitivity and specificity of P-III-P at a cut-off concentration of 12 ng/ml for portal hypertension (portal vein pressure 5 mm Hg) are 0.93 and 0.42, respectively, the diagnostic efficiency is 0.67. Predictive values at the same cut-off level of P-III-P and an assumed prevalence of portal hypertension of 50% are 0.62 and 0.85 for the positive and negative test result, respectively. The level of P-III-P is not related to the degree of esophageal varices. The mean P-III-P concentration in the hepatic vein was found to be significantly (p less than 0.001) higher (about 35%) than that in the cubital vein. It is concluded that P-III-P is not an useful parameter for diagnosis of portal hypertension and monitoring of portal vein pressure and of the degree of esophageal varices.

Catheterization↗
PubMed1988

The predictive value of serum laminin for portal hypertension in chronic liver diseases.

The concentration of laminin, a high molecular weight basement membrane glycoprotein, was determined with a competitive radioimmunoassay in serum from the hepatic and cubital veins of patients with chronic liver diseases (n = 175), and correlated with portal venous pressure calculated from the hepatic vein pressure gradient. The level of laminin in the hepatic vein (mean value: 1.83 U/ml) was significantly (p less than 0.05) higher than that in the cubital vein (mean value 1.68 U/ml). In both vascular regions the glycoprotein levels increased with the degree of fibrosis, reaching their highest concentrations in cirrhosis (2.16 +/- 0.84 U/ml, p less than 0.001) (normal range: 0.81-1.43 U/ml). In all chronic liver diseases there was a significant positive correlation between the level of serum laminin and portal vein pressure (rs 0.70, p less than 0.001), which prompted us to calculate some criteria of the diagnostic validity of raised laminin for portal hypertension (portal venous pressure greater than or equal to 5 mm Hg). At a cut-off concentration of laminin of 1.45 U/ml, sensitivity is 0.87, specificity 0.74, diagnostic efficiency 0.81, and the likelihood ratio 3.4. Positive and negative predictive values at the same cut-off and at a prevalence of portal hypertension in this study of 50% are 0.77 and 0.85, respectively. Serum laminin may prove to be a potentially useful biochemical marker of portal hypertension.

Adult↗
PubMed1987

Estimation of the production rates of serum aminoterminal propeptide of type III procollagen and laminin in human fibrotic liver.

The concentrations of laminin, a high molecular weight non-collagenous glycoprotein of basement membranes, and of the N-terminal propeptide of type III procollagen were determined in the serum of the liver outflow vascular region (hepatic vein) and of a peripheral vein (cubital vein) in patients with chronic liver diseases (fibrosis, cirrhosis, unspecified histology; n = 173), in order to determine their secretion rates from the injured livers. The mean levels of laminin (1.84 kU/l) and of procollagen peptide (28.0 micrograms/l) in hepatic vein were significantly higher (about 9.5% at p less than 0.02, and 37% at p less than 0.001, respectively) than those in the periphery (1.68 kU/l and 20.4 micrograms/l, respectively). In chronic liver diseases, however, laminin and procollagen peptide concentrations in the hepatic vein were lower than or equal to those in the cubital vein in 18% and 27% of patients, respectively. The highest regional differences of the concentrations were noted in cirrhotic subjects. The serum levels of laminin (rs 0.93) and of procollagen peptide (rs 0.73) in hepatic and in cubital vein are highly positively correlated (p less than 0.001), but the levels of procollagen peptide in hepatic vein are only weakly but still significantly statistically related with those of laminin (rs 0.446, p less than 0.001). Similarly, the hepatic-cubital venous concentration differences of both proteins are weakly (rs 0.312) but significantly (p less than 0.001) correlated. On the basis of several assumptions we estimated secretion rates from the livers of 120 U.min-1 for laminin, and 5.7 micrograms.min-1 for procollagen peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1986

Serum concentrations of laminin and aminoterminal propeptide of type III procollagen in relation to the portal venous pressure of fibrotic liver diseases.

In sera of patients with fibrotic liver diseases (n = 33) classified histologically into various degrees of liver fibrosis (n = 21) and cirrhosis (n = 12) the concentrations of the basement membrane protein laminin and of its pepsinresistant fragment P1 and of the N-terminal propeptide of type III procollagen were determined. The concentrations of both proteins were related to the portal venous pressure measured in these patients. Compared with the reference population (n = 146) the concentration of laminin increases from 1.04 U/ml (normal persons) to 1.69 +/- 0.46 U/ml in liver fibrotic and 2.58 +/- 0.87 U/ml in liver cirrhotic patients. Although the concentrations of the propeptide of type III procollagen increase also there exist only weak correlations between both connective tissue proteins in serum. Laminin is correlated highly positive with the portal venous pressure in cirrhotic subjects (r = 0.9206), the extent of laminin elevation reflects closely the degree of portal hypertension. Virtually all of the fibrotic patients having a laminin concentration within the reference range had a normal portal venous pressure. The data suggest laminin as a potentially useful parameter for monitoring the portal venous pressure in cirrhotic and severe fibrotic patients.

Female↗
PubMed1986

Serum laminin--its concentration increases with portal hypertension in cirrhotic liver disease.

The concentrations in serum of the high molecular weight glycoprotein laminin and of the N-terminal propeptide of type III procollagen were determined in various histologically proven fibrotic liver diseases (n = 33), of which the portal venous pressure has been measured indirectly. The concentrations of both biomatrix proteins were related to the portal venous pressure. Laminin in serum of normal persons (n = 146) ranged from 0.81 to 1.43 U/ml. Compared with the mean normal concentration (1.04 U/ml) the glycoprotein is increased in fibrotic liver lesions in parallel with the severity of the fibrotic organ transformation reaching the highest values (2.58 +/- 0.87 U/ml, P less than 0.001) in liver cirrhosis (n = 12). The level of N-terminal propeptide of type III procollagen increased similarly, but the concentrations of both matrix proteins exhibit only weak statistical correlations (r = 0.6680). The level of laminin is correlated strongly with the elevation of the portal venous pressure in cirrhotic (r = 0.9206) and fibrotic (r = 0.7157) subjects. For the propeptide of procollagen the respective correlation is r = 0.4808. Molecular sieve chromatography reveals a heterogeneous composition of laminin-related antigens in serum with two main molecular weight fractions of 700 and 300 kD, respectively.

Adult↗
PubMed1986

Serum concentrations of N-terminal propeptide of type III procollagen and laminin in the outflow of fibrotic livers compared with liver-distal regions.

The immunoreactive serum concentrations of the basement membrane glycoprotein laminin, including its split product (pepsin-resistant fragment P1), and of the aminoterminal propeptide of type III procollagen, were measured in liver outflow (hepatic vein) and in liver-distal venous (renal vein) and arterial (femoral artery) regions in liver cirrhotic and fibrotic patients (n = 40). In the majority of patients with liver fibrosis and cirrhosis (0.52 to 0.69) the relatively highest concentrations of laminin (2.09 U/ml, p less than 0.05) and of procollagen propeptide (28.5 ng/ml, p less than 0.001) were found in the hepatic vein. No significant correlations were observed between the concentrations of the two biomatrix proteins in either region of the circulation, but a highly positive statistical correlation (r = 0.9425) was found between the level of laminin in the hepatic vein of cirrhotic subjects and portal venous pressure. The respective correlations were lower for laminin measured in the renal vein and the femoral artery. The concentration of procollagen propeptide was statistically not related to the portal venous pressure.

Blood Pressure↗
PubMed1982

[Anti-rheumatic therapy in patients with liver diseases. Plasma levels of diclofenac and elimination of diclofenac and metabolites in urine of patients with liver disease].

Ten patients with chronic hepatitis or cirrhotic hepatitis without portal decompensation diagnosed by biochemical, laparoscopical and histological criteria were given 100 mg diclofenac-Na (Voltaren) p.o. in order to evaluate plasma-concentration (0--8 h after application of diclofenac) and urinary excretion of diclofenac resp. hydroxylated metabolites (0--24 h after application). Mean values of the kinetic parameters AUC, Cmax, Tmax and renal excretion were not different as compared to ten healthy controls. Elimination and metabolism of diclofenac was not influenced by the liver diseases. A dose-reduction seems not to be necessary in patients with chronic liver diseases without portal decompensation.

Adult↗
PubMed1982

[New aspects of the pathogenesis of primary biliary cirrhosis, a study of 42 patients (author's transl)].

Studies on 42 patients (38 women, 4 men) with chronic-destructive non-purulent cholangitis or primary biliary cirrhosis demonstrated that the duration of symptoms does not correlate with the histological stages. The shortest duration of symptoms was found in patients in the cirrhotic stage. Enzyme levels measured at the time of diagnosis indicated that--contrary to serum bilirubin and serum copper levels--they did not correlate with the stage of the disease. There was an increased frequency of allergic signs in the past history of this group of patients. Furthermore, in all the women (average age 45) there was a 29% abortion rate. Among the three control groups (no liver disease, chronic-aggressive hepatitis, other forms of liver disease), the one with chronic-aggressive hepatitis also showed a high abortion rate (19.5%).

Abortion, Spontaneous↗
PubMed1982

Validity of monoamine oxidase in serum for diagnosis of liver cirrhosis: estimation of predictive values, sensitivities and specificities.

The validity of monoamine oxidase (EC 1.4.3.4) activity in serum for the diagnosis of fibroproliferative liver disorders was assessed by measuring the specificity, sensitivity and positive and negative predictive values of the enzyme. Enzyme activity was measured in sera of 567 patients including those with biochemically and/or histologically verified non-fibrotic liver diseases (n = 64), liver fibrosis (n = 45), and liver cirrhosis (n = 51). The fraction of liver cirrhotic subjects with pathologically elevated monoamine oxidase activity (greater than 630 U/1) was 0.61, whereas only 0.16 of the cases with liver fibrosis and 0.11 of those with non-fibrotic liver diseases had abnormally high enzyme activities. Among the various categories of diseases tested, significantly increased enzyme activities were confined to liver cirrhosis and chronic active hepatitis. For liver cirrhosis, sensitivities and specificities were calculated as functions of various cut-off (critical) values of monoamine oxidase activity in serum, and with respect to a reference population of healthy men and non-cirrhotic subjects. The predictive value of the positive test result (enzyme activity higher than 720 U/1) at a prevalence of liver cirrhosis of maximum 0.033 (estimated incidence of chronic liver diseases in West Germany) is 0.68 if tested against healthy persons and less than 0.30 if tested against patients with non-liver cirrhotic diseases. It is concluded that monoamine oxidase is probably not helpful in the early diagnosis of fibroproliferative liver dysfunctions but may provide a parameter of complications of cirrhosis, e.g. portal-systemic collateral circulation (portal hypertension).

Chronic Disease↗