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Biomedical subjects

T Propst

Publications and source records attributed to T Propst.

At least 19 recordsLinked to original sources

Carbohydrate malabsorption syndromes and early signs of mental depression in females.

Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart. They were classified as normals, isolated fructose malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose malabsorbers. All patients filled out a Beck's depression inventory-questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4 (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with fructose and lactose malabsorption together (group 4). Isolated fructose malabsorption and combined fructose/lactose malabsorption was significantly associated with a higher Beck's depression score. Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression.

Adult↗

Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination.

Since 1960, hepatitis B virus-associated chronic liver disease has been considered an important problem in dialysis units in both Europe and North America. Separate dialysis facilities for hepatitis B-infected patients, the implementation of universal precautions for the prevention of transmission, and the active immunization against hepatitis B have now reduced the yearly incidence to less than 0.05% in Western countries. However, only 50% to 60% of patients with renal insufficiency develop sufficient immune response after intramuscular hepatitis B vaccination. The aim of the current study was to determine whether the mode of vaccine application plays a role in vaccination response and whether increasing the vaccine dose of primary intradermal hepatitis B vaccination can reduce the number of vaccine injections in hemodialysis patients. We designed a prospective, randomized study of antibody responses to hepatitis B vaccine given intradermally, subcutaneously, or intramuscularly in 81 hemodialysis patients. Outcome measures were rates of seroconversion, mean levels of anti-Hbs antibodies, and antibody levels 8 years after vaccination. The results show that intradermal hepatitis B vaccination response with a higher vaccination dose than previously used in hemodialysis patients is superior to conventional intramuscular and subcutaneous vaccination and is also well tolerated. Five intradermal injections of 20 microg each induced the development of sufficient anti-Hbs antibody titer, which persisted in 70% of the patients over 3 years.

Adult↗

The acute phase protein alpha-1-antitrypsin inhibits transferrin uptake in PLC/PRF/5 cells and increases release of hepatitis B virus surface antigen and alpha-fetoprotein.

BACKGROUND/AIMS: The present study was designed to investigate whether the acute phase protein alpha-1-antitrypsin (alpha1-AT), which has an inhibitory effect on transferrin (tf) receptor-mediated iron uptake in K562 and THP1 cells, has a similar effect in PLC/PRF/5 cells. This hepatic cell line is of specific interest because it is infected with hepatitis B virus (HBV). Therefore, we addressed the additional question whether alpha1-AT has any effect on cellular protein synthesis and replication of HBV in PLC/PRF/5 cells. METHODS: Cells were incubated with various concentrations of alpha1-AT, dexamethasone, IL-6 and desferrioxamine. HBs-AG, alpha-fetoprotein and albumin concentrations in culture media were measured using commercially available methods. For equilibrium inhibition binding experiments, cells were incubated with 85-182 pmol/l [125I]tf. To study the potential effect of alpha1-AT on DNA synthesis we measured the incorporation of [3H]thymidine into DNA. RESULTS: In equilibrium saturation binding experiments, [125I]tf bound to PLC/PRF/5 cells with K(D) 17.45 +/- 4.57 nM and a maximum density of binding sites of 267,285 +/- 39,915 sites/cell. In inhibition studies alpha1-AT demonstrated an apparently monophasic inhibition of [125I]tf to its receptor. At concentrations > 30 micromol/l alpha1-AT inhibited the growth of PLC/PRF/5 cells up to approximately 50%. The inhibitory effect of alpha1-AT on DNA synthesis was not as potent as that on growth. At the highest concentration of 100 micromol/l, alpha1-AT produced a 35% maximum inhibition of [3H]thymidine incorporation. Incubating PLC/PRF/5 cells with corticosteroids enhanced HBs-AG release significantly. Interestingly, alpha1-AT showed the same pattern of effects on cell metabolism and HBs-AG release as the corticosteroids. When we incubated the cells with 50 micromol/l alpha1-AT, alpha-fetoprotein production increased significantly and HBs-AG release almost doubled. CONCLUSION: We have to assume that there is a specific mechanism inducing HBs-AG release by alpha1-AT, as has been shown to be the case with steroids.

Cell Line↗

Evaluation of the developmental toxicities of coumarin, 4-hydroxycoumarin, and 7-hydroxycoumarin using FETAX.

The developmental toxicities of coumarin and hydroxycoumarin metabolites were evaluated using FETAX. Young X. laevis embryos were exposed to coumarin, 4-hydroxycoumarin, and 7-hydroxycoumarin in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO), cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450 activity. The MAS was also treated with cyclohexene oxide (CHO) to selectively modulate epoxide hydrolase activity. Without the MAS or inhibited MAS, coumarin and 7-hydroxycoumarin were nearly equitoxic, whereas 4-hydroxycoumarin was nearly 2-fold less developmentally toxic than coumarin on an equimolar basis. Addition of the MAS and CIM-MAS increased the developmental toxicities of coumarin and, particularly, 4-hydroxycoumarin. Addition of the CHO-MAS greatly increased the developmental toxicity of coumarin and, especially, 4-hydroxycoumarin. Addition of the ELL- or CO-inhibited MAS did not increase the developmental toxicity of coumarin. However, addition of the intact MAS did not alter the developmental toxicity of 7-hydroxycoumarin. Results from these studies suggested that P-450; specifically ELL-inhibited P-450 (arylhydrocarbon hydroxylase) may have been responsible for increasing the developmental toxicity of coumarin. Furthermore, the increased toxicity of coumarin or 4-hydroxycoumarin following co-incubation with CHO-treated microsomes indicated that highly toxic epoxide intermediates may be produced from oxidative P-450 metabolism and that epoxide hydrolase may play a role in detoxification of the reactive intermediates.

4-Hydroxycoumarins↗

Papillitis and vasculitis of the arteria spinalis anterior as complications of hepatitis C reinfection after liver transplantation.

It is well known that hepatitis C virus (HCV)-related chronic liver disease may be associated with various immunological disorders including mixed cryoglobulinemia, which is accompanied by cutaneous vasculitis, arthralgias, membrano-proliferative glomerulonephritis, and neuropathy in association with cryoprecipitable immune complexes in serum. We describe here the first case of central nervous system HCV infection with evidence of the virus in the cerebrospinal fluid in association with cryoglobulinemia in a patient who developed recurrent episodes of papillitis and vasculitis of the arteria spinalis anterior after liver transplantation.

Adult↗

Evaluation of the developmental toxicity of theophylline, dimethyluric acid, and methylxanthine metabolites using Xenopus.

The developmental toxicities of theophylline and theophylline metabolites were evaluated using FETAX (Frog Embryo Teratogenesis Assay - Xenopus). Young X. laevis embryos were exposed to theophylline, 1-methylxanthine, 3-methylxanthine, or 1, 3-dimethyluric acid in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO), cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450 activity. Addition of the MAS and CIM-MAS reduced the developmental toxicity of theophylline. Addition of the ELL- or CO-inhibited MAS did not reduce the developmental toxicity of theophylline. Addition of the intact MAS did not alter the developmental toxicity of 1-methyl- or 3-methylxanthine which were slightly more developmentally toxic on an equimolar basis than theophylline itself. 1, 3-dimethyluric acid was not developmentally toxic at maximum soluble concentrations in 1% (V/V) DMSO. Results from these studies suggested that P-450, specifically ELL-inhibited P-450 (aryl hydrocarbon hydroxylase) may have been responsible for detoxification of theophylline and that 1, 3 dimethyluric acid represented the primary detoxification metabolite of theophylline.

Abnormalities, Drug-Induced↗

Unusual thoracic collaterals of gastro-oesophageal varices in a patient with end-stage liver disease.

Thoracic varices are rare anomalies in patients with liver cirrhosis and portal hypertension. Gastro-oesophageal varices usually drain into the azygos or hemiazygos vein. The case is reported here of an unusual collateral pathway of gastro-oesophageal varices with drainage to the vena anonyma system presenting as lung masses on chest X-ray, which completely resolved after successful liver transplantation.

Collateral Circulation↗

Comparison of the effects of ranitidine effervescent tablets and magnesium hydroxide-aluminium oxide on intragastric acidity. A single-centre, randomised, open cross-over study.

In previous studies measuring intragastric pH in healthy volunteers it was shown that there was a faster onset of action with ranitidine (CAS 66357-35-5) 300 mg effervescent tablets (Zantac) compared to standard tablets. In a single-centre, randomised, open cross-over study the pH-values obtained over 6 h following the administration of one ranitidine 150 mg effervescent tablet were compared with those after aluminium oxide-magnesium hydroxide (algeldrate, CAS 1330-44-5, Al-Mg-hydroxide) 10 ml and placebo in healthy volunteers. 24 healthy male subjects between 19 and 32 years of age entered the study, 19 subjects were available for all three measurements. After an overnight fast, intragastric pH was monitored for 7 h using a glass electrode and a digital data recorder. The time in % during which the pH was > or = 3.5 and the area under the curve of the obtained pH-curves were compared. There was a highly statistically significant difference between ranitidine effervescent tablets versus Al-Mg-hydroxide and placebo whereas there was no such difference between Al-Mg-hydroxide and placebo. The onset of action of ranitidine effervescent tablets was almost immediate. It is concluded that there was a clear superiority of ranitidine effervescent tablets in healthy volunteers and it is suggested that pH-metry in patients with acidity-related diseases should be investigated for a better understanding of the function of effervescent tablets.

Adult↗

[Hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The profile of risk factors associated with HCC includes not only chronic infection with hepatitis B virus and/or hepatitis C virus with subsequent cirrhosis, but also metabolic and alcoholic chronic liver diseases. While the risk of developing cancer is high in patients with cirrhosis, the aim of most screening programmes is to detect small, potentially resectable tumors. Serum alpha 1-fetoprotein lacks both sensitivity and specificity as a screening test and two-thirds of patients with small HCCs have levels below 200 ng/ml. Hepatic resection or liver transplantation at an early stage of HCC, without extrahepatic metastasis, provide complete cure of the disease.

Adult↗

Prognosis and life expectancy in chronic liver disease.

The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.

Autoimmune Diseases↗

Copper-induced acute rhabdomyolysis in Wilson's disease.

Wilson's disease is a lethal defect in copper metabolism causing a continual increase in tissue copper concentrations that become toxic to the liver, brain, kidney, eye, skeletal system, and several other tissues and organs. The liver is unique among these in being both the site of the etiologic biochemical abnormality and the organ that is always affected by copper toxicosis. Although myocardial muscle involvement has been reported in association with Wilson's disease, copper deposits in peripheral muscle tissue have not yet been described. A case of a young patient with Wilson's disease who developed recurrent episodes of acute rhabdomyolysis is presented, and the accumulation of copper in muscle tissue as a possible complication is discussed.

Acetates↗

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases.

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.

Acute-Phase Proteins↗