Guidelines for care of the elderly.
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Accidental Falls↗
Biomedical subjects
D Mayer
Publications and source records attributed to D Mayer.
Enhancement and phenotypic modulation of N-nitrosomorpholine-induced hepatocarcinogenesis by dehydroepiandrosterone.
Hepatocarcinogenesis was induced in male and female rats by continuous administration of the adrenal steroid dehydroepiandrosterone (DHEA; 0.6% in the diet) with and without previous treatment with N-nitrosomorpholine (NNM; 120 mg/l drinking water for 7 weeks). DHEA treatment alone resulted in hepatocellular adenomas (HCA) and carcinomas (HCC) after 72-84 weeks, the incidence of both benign and malignant neoplasms being higher in females than in males. After DHEA administration for up to 32 weeks subsequent to NNM, the incidence of HCA and HCC was significantly higher (HCA, 42%; HCC, 42%) than after NNM alone (HCA, 33%; HCC, 28%). While total tumor incidence was similar in male (63%) and female (60%) rats after NNM treatment alone, it was higher in females (87%) than in males (80%) after NNM/DHEA treatment. The difference between the genders was mainly due to the higher incidence of HCC in females. Morphometric analysis of preneoplastic foci of altered hepatocytes (FAH) yielded that DHEA treatment did not increase the average total number of FAH induced by NNM, but caused a modulation of the phenotype of FAH from the glycogenotic/basophilic to the amphophilic cell lineage. The results confirm that DHEA acts as a hepatocarcinogen and show for the first time that it enhances NNM-induced hepatocarcinogenesis in rats.
Adenoma, Liver Cell↗
Testing the power of belief.
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Controlled Clinical Trials as Topic↗
Dietary alpha-tocopherol prevents dehydroepiandrosterone-induced lipid peroxidation in rat liver microsomes and mitochondria.
Dehydroepiandrosterone (DHEA), an adrenal steroid, causes lipid peroxidation in rat liver microsomes and mitochondria and induces hepatocarcinogenesis. It was investigated whether alpha-tocopherol, a naturally occurring free radical chain terminator, could decrease lipid peroxidation. When DHEA-free diet supplemented with increasing concentrations of alpha-tocopherol (25, 50, 100, 200, 400 and 1000 mg/kg diet) was fed to rats for 7 days, a marked lipid peroxidation (measured as thiobarbituric acid reactive substances formation) was observed at concentrations 25 and 50 mg/kg in liver microsomes and mitochondria isolated from these animals. Lipid peroxidation was significantly reduced at concentrations > or = 100 mg/kg. When DHEA (500 mg/kg diet) was fed to rats simultaneously with increasing concentrations of alpha-tocopherol, strong lipid peroxidation was observed at alpha-tocopherol concentrations < or = 200 mg/kg diet. However, microsomes and mitochondria isolated from livers of rats fed alpha-tocopherol at doses of 400 and 1000 mg/kg diet produced only negligible amounts of thiobarbituric acid reactive substances. The data show that high concentrations of alpha-tocopherol in the diet decrease DHEA-induced microsomal and mitochondrial lipid peroxidation. Our results support the concept that alpha-tocopherol can protect against DHEA-induced lipid peroxidation and consequently against steroid-induced liver cell damage and, perhaps, also tumour development.
Animals↗
Isolated talus fractures: description of a new clinical sign.
Isolated talus fractures are very uncommon and are usually associated with severe trauma. Five cases of isolated talus fracture associated with relatively minor trauma are reported. These five patients had one clinical sign in common, pain out of proportion to the severity of their injury. The treatment of talus fractures is reviewed.
Adult↗
Early bioenergetic changes in hepatocarcinogenesis: preneoplastic phenotypes mimic responses to insulin and thyroid hormone.
Biochemical and molecular biological approaches in situ have provided compelling evidence for early bioenergetic changes in hepatocarcinogenesis. Hepatocellular neoplasms regularly develop from preneoplastic foci of altered hepatocytes, irrespective of whether they are caused by chemicals, radiation, viruses, or transgenic oncogenes. Two striking early metabolic aberrations were discovered: (1) a focal excessive storage of glycogen (glycogenosis) leading via various intermediate stages to neoplasms, the malignant phenotype of which is poor in glycogen but rich in ribosomes (basophilic), and (2) an accumulation of mitochondria in so-called oncocytes and amphophilic cells, giving rise to well-differentiated neoplasms. The metabolic pattern of human and experimentally induced focal hepatic glycogenosis mimics the phenotype of hepatocytes exposed to insulin. The conversion of the highly differentiated glycogenotic hepatocytes to the poorly differentiated cancer cells is usually associated with a reduction in gluconeogenesis, an activation of the pentose phosphate pathway and glycolysis, and an ever increasing cell proliferation. The metabolic pattern of preneoplastic amphophilic cell populations has only been studied to a limited extent. The few available data suggest that thyromimetic effects of peroxisomal proliferators and hepadnaviral infection may be responsible for the emergence of the amphophilic cell lineage of hepatocarcinogenesis. The actions of both insulin and thyroid hormone are mediated by intracellular signal transduction. It is, thus, conceivable that the early changes in energy metabolism during hepatocarcinogenesis are the consequence of alterations in the complex network of signal transduction pathways, which may be caused by genetic as well as epigenetic primary lesions, and elicit adaptive metabolic changes eventually resulting in the malignant neoplastic phenotype.
Animals↗
Hexokinase expression in liver preneoplasia and neoplasia.
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Animals↗
Diagnostic and therapeutic confusion caused by TBG deficiency in an 18 years old adolescent.
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Adolescent↗
Fulminant meningococcal meningitis and sepsis associated with severe hypothyroidism caused by autoimmune (Hashimoto) thyreoiditis.
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Adult↗
Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences.
Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta-oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.
Acyl-CoA Oxidase↗
Eosinophil chemotaxis inhibited by 5-lipoxygenase blockade and leukotriene receptor antagonism.
We studied the effects of the 5-lipoxygenase inhibition and sulfidopeptidyl leukotriene receptor antagonism on lumenal chemotaxis of eosinophils in 124 guinea pig tracheal explant preparations from 62 animals. Cell migration was assessed histologically and by differential cell count, and airway narrowing was measured by calibrated micrometry. Intralumenal instillation of the chemotaxin, formyl-met-leu-phe (FMLP) caused migration of 163,509 +/- 18,103 eosinophils/cm segment (eos/cm) versus 15,443 +/- 3,557 eos/cm for segments receiving vehicle only (p < 0.001). Coincubation of FMLP with zileuton, a selective inhibitor of 5-lipoxygenase, caused a concentration-related inhibition of eosinophil migration. At 10(-10) M zileuton, cell migration caused by FMLP was decreased by 57% and nearly complete reduction to 17,200 +/- 3,620 eos/cm resulted after 10(-6) M zileuton (p < 0.001 versus FMLP). Lumenal narrowing caused by FMLP (15.3 +/- 3.4%) was attenuated maximally to 1.15 +/- 2.51% after 10(-8) M zileuton (p < 0.02). In 36 preparations, concentration of leukotriene B4 (LTB4) was measured in treated tracheal perfusate. LTB4 secretion caused by FMLP was 6.4 +/- 0.48 pg/ml versus 3.32 +/- 0.89 pg/ml for buffer control at 5 min (p < 0.02) and was undetectable 120 min after activation with FMLP. Blockade of LTB4-receptor with the selective antagonist, LTB4 dimethyl amide, caused > 90% inhibition of eosinophil migration (p < 0.001). Comparable results were obtained with zafirlukast, an LTD4-receptor antagonist. Our data demonstrate that both LTB4 and LTD4 facilitate eosinophil migration from lamina propria to lumen caused by the chemotaxin, FMLP, and that LTB4-induced eosinophil migration is accompanied by initial lumenal secretion of LTB4.
Animals↗
Influence of the intensity of NaCl solutions on adaptation degree and recovery time course.
The degree of adaptation and the time course of recovery after adaptation to NaCl solutions of various intensities were examined by magnitude estimation and simple sensory reaction time using a test stimulus of constant intensity. The results show that the degree of adaptation increased with the adapting concentration following a negatively accelerated function. Similarly, all recovery curves were negatively accelerated functions of the recovery time. The relation between the recovery constant (time necessary to attain two-thirds of normal responsivity) and adapting concentration approximates with both criteria more or less a linear function. Thus the recovery constant is a positively accelerated function of the degree of adaptation. The relationship between concentration and degree of adaptation can be approximated by Beidler's equation of taste stimulation, while the time course of recovery can be expressed by an exponential equation that can also be related to Beidler's theory. The two criteria used showed similar deteriorating effects of taste adaptation, indicating that reaction time can also be a useful criterion of the level of sensory responsivity.
Adult↗
Lesions associated with infectious keratoconjunctivitis in alpine ibex.
Following a severe infectious keratoconjunctivitis (IKC) epizootic in free-ranging alpine ibex (Capra ibex ibex) in Switzerland in 1993, 19 animals were examined from six different populations. Mucopurulent exudates, reddened conjunctiva and mononuclear inflammatory cell infiltration in the conjunctiva and the limbic area were observed in mild cases. In more severe cases, lesions ranged from perilimbic neovascularization to corneal edema, erosion, ulceration and neovascularization accompanied by infiltration of neutrophils. Sometimes an iridocyclitis was observed. In the most advanced stages, the cornea was perforated and an anterior synechia was present. Lesions found in ibex affected with IKC indicated a non-generalized, specific ocular disease. The other organs investigated did not show alterations suggestive of changes induced by agents which might cause IKC, including Chlamydia spp. and Mycoplasma. spp. The microbiological findings indicate that Mycoplasma conjunctivae is the primary pathogenic agent causing IKC in this species in Switzerland.
Animals↗
Evaluation of the 13C-methacetin breath test for quantitative liver function testing.
Noninvasive 13C-breath tests are used for the assessment of hepatocellular dysfunction. 13C-methacetin is metabolized in the liver by O-demethylation to 13CO2 and acetaminophen. The aim of the study was to evaluate the 13C-methacetin breath test in comparison to the Child-Pugh score and other quantitative liver function tests (MEGX-test and indocyanin green-clearance). 2 mg/kg 13C-methacetin were orally given to 31 patients with histologically proven liver cirrhosis of different etiology and severity (nine Child A, 13 Child B, nine Child C), ten patients with chronic viral hepatitis and ten healthy volunteers. The increase of exhaled 13CO2 was expressed as delta over baseline (DOB; delta /1000). Different DOB-values were compared as parameters for assessing hepatocellular dysfunction. All breath test parameters analyzed provided an excellent discrimination between cirrhotic and noncirrhotic individuals. The DOB-value at 20 min showed a superior correlation with the Child-Pugh score (r = 0.67) than did MEGX-test or indocyanine green clearance results (r = 0.39 and r = 0.43, respectively). With a cut-off value of < or = 25 delta /1000 at 20 min, sensitivity and specificity to discriminate between cirrhotic and noncirrhotic individuals was 93.5% and 95%, respectively. The 13C-methacetin breath test is a safe and precise quantitative liver function test. Using one single breath sample 20 min after substrate administration, the test discriminates well between cirrhotic and noncirrhotic patients. Its prognostic value remains to be established.
Acetamides↗
Portal vein thrombosis and multiple liver abscesses in Crohn's disease--an example for successful conservative treatment.
We report about a 27-year-old patient with Crohn's disease presenting with two complications; Portal vein thrombosis and multiple liver abscesses. Conservative treatment with antibiotics and percutaneous catheter drainage was successful, the liver abscesses disappeared. 18 months later the patient presented in best condition. Ultrasound showed cavernous transformation of the portal vein system and splenomegaly, discrete esophageal varices were seen by esophagogastroscopy. This is an example for an excellent course under conservative therapy of liver abscesses, on the other hand it is the first reported case of a patient with a combination of portal vein thrombosis and multiple liver abscesses in Crohn's disease.
Adult↗
Quantitation of the cytosolic phospholipase A2 (type IV) in isolated human peripheral blood eosinophils by sandwich-ELISA.
Sandwich enzyme-linked immunosorbent assay (sELISA) was developed for precise quantitation of cytosolic phospholipase A2 (cPLA2 type IV) concentration in isolated human peripheral blood eosinophils as an alternative to semiquantitative chemiluminescent assay employing immunoprecipitation/Western blot analysis. In this assay, monoclonal mouse anti-human cPLA2 antiserum was used as the capture antibody, polyclonal rabbit anti-human cPLA2 antiserum as the secondary antibody, and alkaline phosphatase-conjugated goat anti-rabbit IgG as the tertiary, reporter antibody. Purified human cPLA2 (0-1000 ng/ml) dissolved in Tris-HCl buffered saline was used as the standard protein. The detection limit for cPLA2 in 10(6) eosinophils was 0.109 ng/ml, and coefficients of inter- and intra-assay variation were 4.23% and 7.07%, respectively. There was no cross-reactivity with other (secretory) isoforms of PLA2 (sPLA2 types I-III) either from porcine pancreas, human synovial fluid, or bee venom. In separate studies, the recovery of cPLA2 was > 83% when eosinophil lysate was supplemented exogenously with two different concentrations of cPLA2. From a total protein content of 22.3 +/- 1.7 micrograms/10(6) cells, the baseline concentration of cPLA2 was 0.38 +/- 0.18 ng/10(6) cells in eosinophils obtained from mildly atopic donors. Immunoblotting studies confirmed the complete specificity for the type IV isoform as detected by sELISA. This sELISA method permits the precise quantitative assessment of cPLA2 in nanogram quantities per million cells, which has not previously been possible by immunoblotting analysis.
Animals↗
A new possible parameter for the detection of aneuploidy inducing substances: the analysis of qualitative and quantitative abnormalities of the spindle apparatus.
In the present study, compared to other cytogenetic methods, we measured the number of aneuploid cells directly by analyzing anomalies of the mitotic spindle. Qualitative and quantitative abnormalities of the mitotic spindle apparatus in transformed and non-transformed cell lines in vitro were classified. We treated the different cell lines with well known aneugenic agents as Benomyl and Griseofulvin and investigated the mitotic spindle under different experimental conditions. The spindle apparatus was stained by indirect immunofluorescence and the chromatin was counterstained by fluorescent dyes. The mitotic spindle showed a great sensitivity to the aneuploidy-inducing substances used in our experiments. The spindle-disturbing effect of the tested substances was demonstrated to be dose- dependent. The morphological alterations appeared to be independent of the aneuploidy-inducing test substance used, but showed a relation to the dose and length of treatment. Thus, the analysis of the mitotic spindle may be a useful screening parameter for the detection of aneuploidy-inducing substances and further investigations will provide additional results to specific parameters.
Aneuploidy↗
Increase of lipid peroxidation in rat liver microsomes by dehydroepiandrosterone feeding.
Oral administration of the adrenal steroid dehydroepiandrosterone (DHEA), a peroxisome proliferator and hepatocarcinogen in the rat, caused an increase in NADPH-dependent lipid peroxidation in microsomes isolated from rat liver and kidney cortex, but not from brain. The increase of liver microsomal lipid peroxidation was greater in male than in female rats. the effect of DHEA on lipid peroxidation became discernible after feeding steroid-containing diet (0.6%) to male and female rats for 2 and 3 days and reached maximal levels at 1 and 2 weeks, respectively. The increase of microsomal lipid peroxidation reached a plateau stimulation at 0.05% in the diet. The addition of DHEA in the concentration range 0.1-100 microM to microsomes isolated from control rats had no effect on lipid peroxidation. Furthermore, a significant increase of the endogenous concentration of thiobarbituric acid reactive substances was found in microsomes after DHEA-administration at 0.05% in the diet. These results provide in vivo evidence that DHEA can cause lipid peroxidation in rat liver. Administration of DHEA at 0.6% in the diet for 7 consecutive days also significantly enhanced NADH- and ascorbate-dependent lipid peroxidation in liver microsomes. The DHEA-stimulated rat liver microsomal lipid peroxidation was completely inhibited by EDTA but not by superoxide dismutase, catalase or mannitol applied as OH-radical scavenger. The findings indicate that membrane lipid peroxidation is an early effect of DHEA, and that this process may be involved in the steroid-induced carcinogenesis in rats.
Adenosine Diphosphate↗