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Biomedical subjects

E Walter

Publications and source records attributed to E Walter.

At least 55 records · Page 3Linked to original sources
PubMed1996

HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans.

The diverse secretory and absorptive functions of the intestinal epithelium are conducted by a mixed population of absorptive cells and mucus-producing goblet cells as the major cell types. In order to approach the main characteristics in an in vitro model, a coculture system of absorptive Caco-2 cells and mucus-secreting HT29-MTX cells was developed and the permeability of a range of different drugs was tested. Variable goblet cell frequency can be achieved, preserving a significant barrier to drug transport and maintaining the differentiated features of both cell types. Absorption rates for actively transported drugs are rather underestimated in the cell culture model when compared to in vivo data. However, a good correlation with fraction absorbed in humans was attained separating the range of passively transported drugs into two groups of well-absorbable compounds with Peff > or = 10 x 10(-6) cm/s and drugs that are absorbed 40-70% with Peff = 0.1-1 x 10(-5) cm/s. A permeability of Peff < 0.1 x 10(-5) cm/s is suggested for low absorbable drugs.

Animals↗
PubMed1996

-Severe hemobilia after percutaneous transhepatic biliary drainage. Successful treatment by arterial catheter embolization-.

We report on an 44-year-old man with Billroth-I-reoperation and transformation into Roux-Y-anastomosis, which was performed because of ulcer-relapse. The postoperative course was complicated by obstructive jaundice and cholangitis. Ultrasound and computed tomography could not clarify the cause. The subsequently performed percutaneous transhepatic cholangiography showed several small concrements in the biliary tract. For decompression of the dilated bile ducts percutaneous transhepatic biliary drainage was applied. Following that the patient developed recurrent episodes of hemobilia, which made the transfusion of altogether 17 units of blood necessary. Angiography clarified the bleeding source showing leakage of the right hepatic artery. By means of repeated selective transcatheter embolization definite hemostasis was achieved. Transcatheter embolotherapy is recommended as initial treatment to control serious iatrogenic hemobilia.

Adult↗
PubMed1995

A new approach to selection and weighting of items in evaluative composite measurement scales.

Evaluative composite measurement scales (CMS) are increasingly used in medicine to measure complex constructs in the absence of a reference criterion or 'gold standard'. However, the level of measurement provided by these instruments has usually been given little attention. This paper explores the influence of the characteristics of the item set and weighting on the level of measurement of an evaluative CMS. The approach is illustrated with an application to the scoring system of the Nottingham Health Profile. Simulations are provided to indicate when the composite score of item responses, on an ordinal or pass-fail scale, could be considered to achieve the properties of an interval scale.

Data Interpretation, Statistical↗
PubMed1995

Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care.

OBJECTIVE: To determine if the use of influenza vaccine in children in day care decreases the incidence of otitis media during the influenza season. DESIGN: Prospective cohort study. SETTING: Eight day-care centers in North Carolina. PARTICIPANTS: One hundred eighty-six children aged 6 to 30 months. INTERVENTION: Half the participants received trivalent subvirion influenza virus vaccine. MEASUREMENTS: Acute otitis media (AOM) and serous otitis media (SOM) were assessed biweekly from mid-November 1993 to mid-March 1994 by visual and tympanometric examinations performed by "blinded" observers. The winter season was divided into three periods-before, during, and after influenza season--and the number of children with AOM or SOM during each period was determined. Unadjusted and adjusted odds ratios (ORs) were computed, while controlling for race and sex using logistic regression methods. RESULTS: Influenza vaccine was protective against AOM (OR = 0.69, 95% CI, 0.49-0.98) during the influenza season. Although there may have been some protection against SOM (OR = 0.75, 95% CI, 0.54-1.02) statistical significance was not achieved. Myringotomy tubes were also significantly protective against AOM and SOM during all three time periods, with ORs between 0.34 and 0.52, but the greatest protection was seen during the influenza period. CONCLUSIONS: Influenza vaccination of 6- to 30-month-old children in day care was associated with a decreased incidence of otitis media during the influenza season. Myringotomy tubes protected against AOM and SOM during all 16 weeks monitored.

Acute Disease↗
PubMed1995

Transepithelial transport properties of peptidomimetic thrombin inhibitors in monolayers of a human intestinal cell line (Caco-2) and their correlation to in vivo data.

Peptidomimetic thrombin inhibitors (TI), derived from L-Asp-D-Phe were examined in confluent monolayers of a human colon carcinoma cell line (Caco-2) to elucidate their transepithelial transport properties. Effect availabilities, based on activated partial thromboplastin time (aPTT) measurements in rats, after peroral administration of five TI correlated reasonably well with permeability coefficients obtained from in vitro transport studies in Caco-2 monolayers, whereas physicochemical properties, such as molecular mass, solubilities, pKa and octanol-buffer partition coefficients failed to yield meaningful relationships. Substitution of the beta-carboxylic group of L-Asp leads to analogues which are mainly transported by passive diffusion, while an unsubstituted carboxylic group favours carrier-mediated active transport. The effects of concentration, temperature, competitive inhibitors and direction dependence on in vitro transport were investigated. The results obtained are compatible with a saturable carrier-mediated transport, operating parallel to a passive paracellular route. The Michaelis-Menten parameters for the active transport component (Km = 1.67 mM, Vmax = 26.5 pmol min-1 mg protein-1) indicate an involvement of the intestinal di/tripeptide transport system for one of the TI. The Caco-2 transport model may be helpful for the design of perorally active peptidomimetics.

Biological Availability↗
PubMed1994

[Hepatitis E--epidemiology and clinical aspects].

Hepatitis E virus (HEV) is a newly identified and molecularly characterized RNA virus. HEV has a worldwide distribution. Large epidemics were observed on the Indian subcontinent, in Central and in Southeast Asia. The enterically transmitted HEV infection also occurs in sporadic form. Only few cases of HEV infection with clinically apparent hepatitis were diagnosed in Western Europe and in the USA. HEV infection causes symptoms of a self-limiting, acute, icteric disease similar to those of hepatitis A. Severe and fulminant courses occur more often than with HAV infection. Chronic liver disease or persistent viremia have not been observed. Diagnosis of HEV infection is based on the detection of anti-HEV-antibodies.

Asia↗
PubMed1994

[Hepatic coma].

The term "hepatic encephalopathy" describes the neuropsychiatric signs and symptoms of patients with acute or chronic liver disease, irrespective of the presence or absence of liver cirrhosis. Cerebral edema, the pathophysiology and treatment of which being quite different from hepatic encephalopathy, is the leading cause of death in patients with acute liver failure. Lactulose (orally or as enema) is one of the cornerstones of the treatment of hepatic encephalopathy; most important for the management of patients with cerebral edema is close monitoring (including intracranial pressure monitoring) of the patients and rapid reduction of intracranial pressure (e.g. with mannitol). The pathophysiologic and therapeutic concepts in the care of patients with hepatic encephalopathy and cerebral edema are described.

Blood-Brain Barrier↗
PubMed1994

Optimal experimental design and therapeutic drug monitoring.

A simple example of intravenous theophylline therapy is used to present and compare various drug administration policies based on stochastic control theory. The simplest approach (Heuristic-Certainty-Equivalence (HCE) control) assumes that the model parameters are known. Prior uncertainty on these parameters can be taken into account by using average optimal (AO) control. The available knowledge about the system can be improved by measuring the drug concentration some time after the beginning of the treatment. This corresponds to the notion of feedback and leads to the HCE feedback (HCEF) and AO feedback (AOF) policies. A further step towards optimality consists in choosing the optimal measurement time given that the final purpose is the control of the system and not the estimation of its parameters. Finally, closed-loop optimal (CLO) control optimally chooses both the dosage regimen and measurement time.

Drug Administration Schedule↗
PubMed1994

Induction of autoimmune phenomena in patients with chronic hepatitis B treated with gamma-interferon.

All interferons display antiviral properties, but gamma-interferon especially has an immunomodulatory effect and may induce autoimmune phenomena. Therefore the formation of autoantibodies was investigated in patients with chronic hepatitis B treated with gamma-interferon. Eleven patients (all HBs-Ag and HBe-Ag positive) were treated for 6 months with recombinant gamma-interferon. The following antibodies were tested: anti-nuclear antibodies, smooth muscle antibodies, anti-actin, anti-mitochondrial antibodies of subgroup anti-M2 and anti-M9 as well as naturally occurring antibodies, antibodies to liver-kidney microsomes, vascular endothelial cell antibodies, sarcolemmal antibodies, parietal cell antibodies, thyroglobulin antibodies and antibodies to laminin and keratin. All patients produced autoantibodies during therapy. The maximum antibody formation and the highest titres were observed in the period between the 3rd and 6th month after therapy began. The cumulative frequencies of the different antibody specificities were as follows: n = 6 anti-nuclear antibodies, n = 7 smooth muscle antibodies, n = 1 anti-actin, n = 12 antibodies to laminin or keratin, n = 6 endothelial cell antibodies/sarcolemmal antibodies, n = 6 anti-mitochondrial antibodies, n = 1 antibodies to liver-kidney microsomes, n = 2 thyroglobulin antibodies, n = 4 parietal cell antibodies. Antibodies persisted in six patients over a period of 3 months (two cases of parietal cell antibodies and one case of antibodies to liver-kidney microsomes) and were still detectable in three patients 6 months after therapy. In three patients new antibody formation occurred 1 month after therapy. So far, clinical signs of an autoimmune disorder have not appeared in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Transepithelial transport and metabolism of thyrotropin-releasing hormone (TRH) in monolayers of a human intestinal cell line (Caco-2): evidence for an active transport component?

Cell culture models for gastrointestinal transport and metabolism are important mechanistic tools. Our studies of Caco-2 monolayers demonstrate heterogeneity in transport characteristics depending on passage number and origin of the cells. In accordance with data obtained in animals and humans, TRH shows a carrier-mediated, saturable transport component, which operates parallel to a passive pathway in Caco-2 cells at passage number 89-99. At low TRH concentrations (< 3 mM) active transport becomes prominent, as demonstrated by the temperature dependence of TRH transport and inhibition experiments. The Michaelis-Menten parameters of the active, saturable transport component are: Km = 1.59 mM and Vmax = 1.84 microM/min. The pH optimum was determined to be at pH 6.0. On the other hand an exclusively paracellular passive route was found with Caco-2 cells at passage number 30-34. These results are also in agreement with observations made by others in cell culture experiments. The aspect of rigorously characterizing the specific Caco-2 clone under investigation is emphasized, especially when active transport mechanisms are suspected.

Amino Acid Sequence↗
PubMed1994

Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic domain.

Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products which have constitutive tyrosine kinase activity and can induce erythroleukemia but not sarcomas. We have previously found that a valine-to-isoleucine point mutation at position 157 (V157I mutant) within the tyrosine kinase domain of this truncated erbB can dramatically activate the sarcomagenic potential of the oncogene and increase the kinase activity of this oncoprotein. This mutation lies at position 157 of the insertionally activated c-erbB product, affecting a highly conserved valine residue of the glycine loop involved in ATP binding and phosphate transfer. To investigate the functional importance of this residue in the catalytic activity of kinases, we have introduced at this position, by site-directed mutagenesis, codons representing the remaining 18 amino acid residues. Most of the mutants have diminished activity, with six of them completely devoid of kinase activity, indicating the sensitivity of this region to conformational changes. Some of these mutants displayed increased kinase activity and greater transforming potential in comparison with IA c-erbB, but none had levels as high as those of the V157I mutant. In general, the sarcomagenic potential of the various erbB mutants correlated with their autophosphorylation state and their ability to cause phosphorylation of MAP kinase. However, there are important exceptions such as the V157G mutant, which lacks enhanced autophosphorylation but is highly sarcomagenic. Studies of this and other autophosphorylation site mutants point to the existence of an autophosphorylation-independent pathway in sarcomagenesis. The requirement for leukemogenic potential is much less stringent and correlates with positivity of kinase activity. When the valine-to-isoleucine substitution was put in context of the full-length erbB protein, the mutation relaxed the ligand dependence and had a positive effect on the transforming potential of the full-length c-erbB.

Animals↗
PubMed1993

[Bacterial infections following sclerosing therapy for esophageal varices].

Two patients with infectious complications 3 and 5 days after elective sclerotherapy of esophageal varices are presented. Both patients had liver cirrhosis (primary biliary cirrhosis and alcoholic liver cirrhosis with hepatitis B virus infection respectively). In one patient a brain abscess developed which was treated successfully by antibiotics and surgery; in the other patient pneumococcal bacteremia and gonarthritis developed. Frequency, possible causes and antibiotic prophylaxis are discussed.

Adult↗