Biomedical subjects
Publications and source records attributed to E Lotterer.
A young girl with cerebral echinococcosis was treated with albendazole (13 mg/kg/d, p.o.). The concentrations of albendazole sulphoxide were determined in serum, cerebrospinal fluid and hydatidous cyst over a month. The mean ratios of concentration were: CSF/serum = 50%, cyst/serum = 40%, cyst/CSF = 80%.
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The 13C-urea breath test (13C-UBT) for diagnosis of Helicobacter pylori (Hp) infection was evaluated in 41 patients after partial gastrectomy and was used for determination of the Hp-prevalence after two different procedures of reconstruction of the gastrointestinal tract, i.e. Billroth's II operation and Roux-en-Y anastomosis. Breath samples were taken at various time points within 30 minutes after a motility inhibiting liquid test meal with citric acid followed by 75 mg of 13C-urea. The 13CO2/12CO2-ratio (delta-value) was measured using isotope ratio mass spectrometry and the recovery of tracer in the exhaled breath was calculated (UBT-value). In all patients and in the corresponding control groups comparison of established reference methods (culture, CLO test, and Fuchsin staining) with the 4 point breath analysis for detection of Hp was investigated. In patients with partial gastrectomy, the sensitivity of the 13C-UBT to detect the presence of Hp and the negative predictive values were 100%, whereas the specificity and the positive predictive values were about 80%. In patients without gastric surgery quality control parameters were not significantly different. Hp-prevalence in postoperative patients was about 45%. All results were independent of their expression either as delta-value or as UBT-value and were not significantly different between the patients with Billroth's II operation and the patients with Roux-en-Y anastomosis. In conclusion, the 13C-UBT is a suitable method for diagnosis and therapeutic monitoring of Hp-status in patients after partial gastrectomy.
Visual event-related P300 potentials, conventional visual evoked potentials, and psychometric tests were applied to patients with noncirrhotic chronic liver disease and to clinically nonencephalopathic and encephalopathic cirrhotics to compare their diagnostic efficacy in detecting early portosystemic encephalopathy (PSE). Sixty-four investigations were performed in 58 patients. The latencies of the P300 parameters were significantly longer in both the encephalopathic and nonencephalopathic cirrhotics than in the noncirrhotics, indicating distinctly abnormal cortical processing of visual stimuli in cirrhotic patients. The visual P300 potentials showed the highest sensitivity and specificity for grade I PSE. Abnormal P300 test results were also found in 78% of the clinically nonencephalopathic cirrhotics, while psychometric tests showed abnormalities in only 41%. The P300 latencies were similar in alcoholic and nonalcoholic cirrhotics. Significant inverse correlations were found between the P300 latencies and measures of quantitative liver function such as galactose-elimination capacity and aminopyrine breath test. It is concluded that visual event-related P300 potentials are a sensitive index of subclinical and grade I PSE. Furthermore, the degree of cognitive dysfunction detected by this method in patients with liver cirrhosis appears to be related to the reduction in hepatic metabolic capacity.
In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab-fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 +/- 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 +/- 1.5, n.s.) with only slight evidence for inflammation: GOT 28 +/- 22 vs. 24 +/- 21 U/l; GPT 24 +/- 23 vs. 31 +/- 28 U/l; gamma-globulins 24 +/- 8 vs. 22 +/- 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 +/- 19 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites.
Various methods of gentamicin dosing were compared in order to evaluate factors that prevent achievement of therapeutic peak and trough plasma concentrations in every patient. When standard doses of 3 x 80 mg of gentamicin/day (i.e., 3 x 170 mumol/day) were administered, only 26% of peak and 51% of trough plasma concentrations were within the desired range. This percentage increased for peak levels to 54% (p less than 0.001) when physicians were instructed in the use of a programmed pocket calculator (PPC) and to 70% (p less than 0.001) when in addition the nursing staff was trained. The best results were achieved when dosing and blood sampling were supervised by a single trained person, 76% of initial peak and 71% of initial trough levels being within the therapeutic range. In this group of patients, further dosage adjustments by the PPC achieved 92% of peak levels in the desired range, while no patient had elevated trough levels. Analysis of the factors that led to these results revealed that neither the laboratory nor the PPC are limiting factors for optimal results. The goal of therapeutic plasma concentrations can be achieved, but requires appropriate attention to the accuracy of blood sampling and dosing. For this purpose, a special program, i.e., more than ordinary attention to drug therapy, is needed.
The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations greater than 1 mumol.l-1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.
A 13C-urea breath test for detection of Helicobacter pylori infection was validated in 306 patients. Breath samples (four, two or one) were taken at various time points within 30 minutes after a motility inhibiting liquid test meal with citric acid followed by 75 mg of 13C-urea. The 13CO2/12 CO2-ratio (delta-value) was measured using isotope ratio mass spectrometry and the recovery of tracer in the exhaled breath was calculated (UBT-value). In 172 patients a comparison of established reference methods (culture, CLO test, and Fuchsin staining) with the 4 point breath analysis for detection of Helicobacter pylori showed high values of quality parameters (greater than 80% for sensitivity, specificity, positive and negative predictive value), independent of expression of the results as delta-value or as UBT-value. In 134 patients a reduction of samples to one single breath sample taken 30 minutes after ingestion of the tracer showed no significant differences in the quality parameters when compared with the standard 4 point breath analysis. This indicates that the analysis of a single breath sample is suitable for detection of Helicobacter pylori status in man.
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Ursodeoxycholic acid treatment of patients with primary biliary cirrhosis may lead to relief of pruritus and improvement of biochemical liver tests. The changes in serum and urinary bile acids induced by ursodeoxycholic acid treatment were studied. After 29 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (750 to 1,000 mg/day) for 6 to 12 mo because of an increase in ursodeoxycholic acid, total plasma bile acids increased from 30.5 +/- 6 mumol/L (mean +/- S.E.M.) to 52.7 +/- 11.7 mumol/L (p less than 0.01). The increase in total plasma bile acids correlated significantly with concentrations of plasma bile acid before treatment (p less than 0.01). The concentrations of endogenous bile acids decreased, mainly because of a decrease of cholic acid. During treatment, glycine conjugation increased and taurine conjugation decreased, whereas sulfation and glucuronidation of bile acids were unchanged. In 10 patients with primary biliary cirrhosis in stages III and IV, urinary excretion of bile acids was also studied. After treatment, ursodeoxycholic acid and its 3-beta isomer and C-1-hydroxylated and C-6-hydroxylated derivatives were also excreted. During treatment, urinary excretion of endogenous bile acids decreased. The increase of ursodeoxycholic acid and the decrease of endogenous bile acids may both be related to the improvement of biochemical liver tests in precirrhotic stages of the disease. In cirrhosis, endogenous bile acids in plasma remained high and changes in liver tests were small.
In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.
A 66-year old woman presented all the features of primary biliary cirrhosis and the blue rubber bleb naevus syndrome. This case represents a new association of primary biliary cirrhosis with an inherited disease.