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Biomedical subjects

P Bauerfeind

Publications and source records attributed to P Bauerfeind.

At least 55 records · Page 3Linked to original sources

Is virtual colonoscopy a cost-effective option to screen for colorectal cancer?

OBJECTIVE: Computed tomography (CT) or magnetic resonance (MR) colonography is a new technique that uses data generated from CT or MR imaging to create two- and three-dimensional scans of the colon. It has been advocated to become the new primary technique of screening for colorectal cancer. The economic feasibility of such recommendation, however, has not yet been evaluated. METHODS: The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found. RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spent on colonoscopy screening. The incremental cost-effectiveness ratios comparing CT colonography to no screening and colonoscopy to CT colonography were $11,484 and $10,408, respectively. Screening by colonoscopy remains more cost-effective even if the sensitivity and specificity of CT colonography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs 54% less than colonoscopy. CONCLUSIONS: To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better than those associated with colonoscopy.

Adult↗

Detection of mass lesions with MR colonography: preliminary report.

PURPOSE: To evaluate the performance of magnetic resonance (MR) colonography in the detection of colorectal mass lesions. MATERIALS AND METHODS: Twenty-three patients underwent MR colonography preceding colonoscopy. The colon was filled with a gadolinium-water mixture (1:100) with MR imaging guidance, and the patient was imaged prone and supine with a breath-hold three-dimensional spoiled gradient-recalled sequence. In addition, two-dimensional spoiled gradient-recalled images were acquired before and after intravenous administration of gadopentetate dimeglumine. Images were interactively analyzed on the basis of multiplanar reconstruction by two radiologists. For regions that were not conclusively assessable with multiplanar reconstruction, virtual intraluminal endoscopic images of the colon were reconstructed. MR findings were correlated with colonoscopic results. RESULTS: Two patients were excluded from the analysis. Findings in eight of 11 patients were correctly assessed as normal and in six of 10 as mass-positive. In the four patients with false-negative findings, one had two 8-mm polyps and the other three had polyps smaller than 5 mm. All nine mass lesions larger than 10 mm, as well as four of the 10 polyps ranging between 5 and 10 mm, were detected, but all polyps smaller than 5 mm were missed. In contrast to the polyps less than 5 mm, the four missed polyps (5-10 mm) could be identified retrospectively on virtual intraluminal endoscopic images. Contrast enhancement was documented in 13 polyps. CONCLUSION: Three-dimensional MR colonography provided virtual colonoscopic viewing and helped detection of colonic polyps.

Adult↗

Preliminary assessment of three-dimensional magnetic resonance imaging for various colonic disorders.

BACKGROUND: Improvements in magnetic resonance imaging (MRI) technology have enabled the acquisition of three-dimensional MRI datasets in a single breath hold. We adopted this technique to make a three dimensional intraluminal and extraluminal assessment of the colon in three patients with various colonic disorders. METHODS: One patient was studied after having a double-contrast barium enema. Two patients had MRI scans after colonoscopy, which showed three colonic tumours in one and multiple polyps in the ascending colon of the other. The process of rectal filling with 1.5-2.0 L water mixed with 15-20 mL 0.5 mol/L gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) was monitored with MR fluoroscopic sequence. Three-dimensional datasets of the contrast-filled colon were taken with patients in prone (before and after intravenous administration of 0.1 mmol/kg bodyweight Gd-DTPA) and supine positions. 64 sections with a voxel-resolution of 2.0 x 2.0 x 1.25 mm3-were taken during a 28 s breath hold. Three-dimensional maximum intensity projection, multiplanar reconstruction, and virtual colonoscopic images of the colon were created from these. FINDINGS: Analysis of the coronal source images in conjunction with multiplanar reconstructions revealed all relevant abnormalities, including diverticula, carcinomas, and polyps. Three dimensional maximum-intensity projections gave a morphological overview of the whole colon. Targeted projections, made up of a limited number of coronal source images, showed diverticula and smaller polyps more clearly. After patients were given intravenous contrast all colonic mass lesions were enhanced. Datasets obtained in prone patients gave the best intraluminal views of the colon. Virtual magnetic resonance colonoscopy showed colonic haustra as well as the ileocaecal valve, but did not show clearly the diverticula. All intraluminal mass lesions, on the other hand, were easy to see. INTERPRETATION: The potential of three-dimensional colonic MRI to provide accurate, minimally invasive, cost-effective polyp screening, as well as comprehensive colonic tumour staging, warrants further investigation.

Aged↗

Virtual colonoscopy with magnetic resonance imaging: in vitro evaluation of a new concept.

BACKGROUND & AIMS: Screening for colonic polyps is desirable. A new concept based on cross-sectional and endoscopic analysis of a magnetic resonance (MR) data set is presented. METHODS: Ex vivo autopsy colonic specimens, containing artificially placed polyps, were obtained and filled with a gadolinium-containing solution. Forty-four thin-section MR images were obtained in a 1.5-T MR scanner in 28 seconds. A three-dimensional endoscopic fly-through of these images was rendered. Fly-throughs and two-dimensional cross-sectional images were analyzed by two observers for the presence of polyps. RESULTS: The average sensitivity and specificity for the detection of polyps based on three-dimensional endoscopic MR colon imaging were 87% and 96%, respectively. Analysis of cross-sectional images showed an overall sensitivity and specificity of merely 57% and 84%, respectively. The difference in the interpretation of three-dimensional MR colonoscopy and two-dimensional cross-sections was statistically significant (P < 0.001). With three-dimensional MR colonoscopy, overall sensitivity for detection of polyps measuring < or =5 mm in length and diameter was 70%; for larger polyps, it increased to 95% (P < 0.01). CONCLUSIONS: The feasibility of an MR-based endoluminal assessment of the colon is shown. Minimal invasiveness, lack of radiation exposure, and high in vitro diagnostic accuracy warrant further investigation of this novel concept.

Colonic Polyps↗

[3D MRI of the colon: methods and initial results].

PURPOSE: "Exoscopic" and endoscopic identification of colorectal pathologies via MRI. METHODS: 5 patients (36-88 years), two normal and three with different colorectal pathologies (diverticular disease, polyps and carcinoma of the colon), were examined by MRI after colonoscopy. Subsequent to filling of the colon with a gadolinium-water mixture under MRI-monitoring, 3D-data sets of the colon were acquired in prone and supine positions over a 28 sec breath hold interval. Subsequently multiplanar T1-weighted 2D-sequences were acquired before and following i. v. administration of Gd-DTPA (0.1 mmol/kg BW). All imaging was performed in the coronal orientation. The 3D-data were interactively analysed based on various displays: maximum intensity projection (MIP), surface shadowed display (SSD), multiplanar reconstruction (MPR), virtual colonoscopy (VC). RESULTS: All of the colorectal pathologies could be interactively diagnosed by MPR. On MIP images some pathologies were missed. VC presented the morphology of colon haustra as well as of all endoluminally growing lesions in a manner similar to endoscopy. The colon masses showed uptake of contrast media and could thus be differentiated from air or faeces. CONCLUSION: The potential of CMRI in colorectal diagnosis warrants further investigation in a larger series of patients.

Aged↗

Synthesis and activity of Helicobacter pylori urease and catalase at low pH.

BACKGROUND: Helicobacter pylori produces large amounts of urease presumably to be prepared for the rare event of a sudden acid exposure. The hypothesis that H pylori is acid sensitive and protein production is inhibited by low pH was examined. METHODS: H pylori or its soluble enzymes were incubated buffered or unbuffered at a pH ranging from 2-7 in the presence of 5 mM urea for 30 minutes. After exposure, urease and catalase activities of whole cells, supernatants, and soluble enzyme preparations were measured at pH 6.8. Newly synthesised enzyme was quantified by immunoprecipitation of [35S]-methionine labelled protein. RESULTS: Exposure to buffer below pH 4 resulted in loss of intracellular urease activity. In soluble enzyme preparations and supernatant, no urease activity was measurable after incubation at pH < 5. In contrast, catalase in whole cells, supernatant, and soluble enzyme preparations remained active after exposure to pH > or = 3. Exposure below pH 5 inhibited synthesis of total protein including nascent urease and catalase. At pH 6 or 7, urease represented 10% of total protein, catalase 1.5%. Exposure of H pylori to unbuffered HCl (pH > 2) resulted in an immediate neutralisation; urease and catalase activities and synthesis were unchanged. CONCLUSION: Low surrounding pH reduces activity of urease and synthesis of nascent urease, catalase, and presumably of most other proteins. This suggests that H pylori is not acidophilic although it tolerates short-term exposure to low pH.

Bacterial Proteins↗

[Peptic ulcer, Helicobacter pylori].

The etiology of gastric or duodenal ulcer defines the choice of treatment. In patients with H. pylori infection but without NSAID treatment of the acute ulcer is achieved by a one week eradication therapy. Prolonged treatment with acid inhibitors is usually not necessary. Eradication should be done by a triple therapy consisting of one acid inhibitor and two antibiotics. Success of the eradication should be controlled 4 weeks after end of the treatment by a C13-urea breath test. Serology is not useful for this matter. NSAID induced ulcers without H. pylori infection should be treated for 4-6 weeks with a potent acid inhibitor, preferably a proton pump inhibitor. If NSAID is continued afterwards prophylaxis against ulcer relapse is necessary. Prostaglandin analog Misoprostol is the only well established drug for that. Proton pump inhibitors seemed also to prevent NSAID ulcer, but solid publications are lacking. H. pylori and NSAID are independent risk factors. Thus. H. pylori eradication does not necessarily prevent relapse of NSAID induced Ulcers. Relapse prophylaxis by Misoprostol or possibly by PPI seems advisable. Ulcer without H. pylori infection and without NSAID is seldom. Other reasons, such as carcinoma, Whipple's disease or Zollinger-Ellison syndrome has to be ruled out. False negative H. pylori tests should be excluded by searching for H. pylori with other methods.

Anti-Bacterial Agents↗

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomach in vitro.

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO2 and bicarbonate whereas, during normal acid, secretion cytoprotective CO2/HCO3- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in an in vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO2 supply. Without acid inhibition there was no mucosal damage at any level of serosal CO2/HCO3- supply. Acid inhibition reduced metabolic CO2 production by 29% (P < 0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P < 0.05). Although, 1% CO2 supply completely replaced the reduction in metabolic CO2, it did not protect against mucosal damage. Overreplacement by 5% serosal CO2/HCO3- was required to prevent damage. There was no correlation between luminal CO2/HCO3- output and mucosal damage. The protection by endogenous or exogenous CO2/HCO3- appears to act intracellularly rather than by intragastric or intercellular neutralization.

Acid-Base Equilibrium↗

Allelic exchange mutagenesis of nixA in Helicobacter pylori results in reduced nickel transport and urease activity.

Helicobacter pylori, an etiologic agent of gastritis and peptic ulceration in humans, synthesizes urease, a nickel metalloenzyme, as its most abundant protein. NixA, a high-affinity nickel transport protein, allows synthesis of catalytically active urease when coexpressed with H. pylori urease in an Escherichia coli host. To determine whether NixA is essential for the production of active urease in H. pylori, nixA was insertionally inactivated with a kanamycin resistance cassette (aphA) and this construct was electroporated into H. pylori ATCC 43504; allelic exchange mutants were selected on kanamycin-containing medium. The nixA mutation, confirmed by PCR, reduced urease activity by 42% (140 +/- 70 micromol of NH3/min/mg of protein in the mutant versus 240 +/- 100 micromol of NH3/min/mg of protein in the parent (P = 0.037). Rates of nickel transport were dramatically reduced (P = 0.0002) in the nixA mutant (9.3 +/- 3.7 pmol of Ni2+/min/10(8) bacteria) of H. pylori as compared with the parent strain (30.2 +/- 8.1 pmol of Ni2+/min/10(8) bacteria). We conclude that NixA is an important mediator of nickel transport in H. pylori. That residual nickel transport and urease activity remain in the nixA mutant, however, provides evidence for the presence of a redundant transport system in this species.

Alleles↗

Regulation of murine acid secretion by CO2.

To determine whether endogenous metabolic sources alone provide sufficient CO2 for acid secretion in mammals, basal and stimulated acid secretion and metabolic CO2 production were measured concurrently in mouse stomachs, in vitro, without exogenous CO2, and after addition of 5% CO2 serosally. Basal acid secretion was varied by changing luminal pH from 3.2 to 4.0. In the absence of an exogenous supply of CO2 acid secretion was stable under basal conditions and increased during cholinergic stimulation with carbachol. Serosal CO2 supply increased basal and stimulated acid secretion. The increase in basal acid secretion depended on the initial level of acid secretion. At pH 4.0, exogenous CO2 increased acid output (mean +/- SD) by 13% from 112 +/- 11 nmol/min to 126 +/- 8 nmol/min (P < 0.03), whereas at pH 3.6 the increase was 40% (63 +/- 14 to 88 +/- 20 nmol/min, P < 0.04) and 157% at pH 3.2 (21 +/- 13 to 54 +/- 14 nmol/min, P < 0.002). Following cholinergic stimulation a maximal acid output of 321 +/- 38 nmol/min was attained without serosal CO2, whilst addition of 5% CO2 to the serosal solution increased maximal acid secretion by 49% to 479 +/- 96 nmol/min (P < 0.005). Metabolic activity, measured as total gastric CO2 production, was greater as acid secretion rates increased [239 +/- 20 nmol/min at 21 +/- 13 nmol/min (luminal pH 3.2) versus 406 +/- 28 nmol/min at 321 +/- 17 nmol/min (after cholinergic stimulation)]. The data support the concept that basal and sub-maximal acid secretion can be maintained by CO2 available from metabolic sources, but full expression of the acid secretory apparatus requires exogenous CO2.

Animals↗

Helicobacter pylori nickel-transport gene nixA: synthesis of catalytically active urease in Escherichia coli independent of growth conditions.

Urease is a virulence determinant, a taxonomic and diagnostic marker, and immunogen for Helicobacter pylori, an aetiologic agent of gastritis and peptic ulceration. This enzyme requires Ni2+ ions in the active site for successful hydrolysis of urea. When expressed in Escherichia coli, recombinant urease is only weakly active unless urease structural subunits are overexpressed, exogenous NiCl2 is added, and the host strain is grown in medium that does not chelate free Ni2+. As wild-type H. pylori does not require such conditions for very high levels of urease expression, we reasoned that additional genes were required to accumulate the metal ion. To isolate such genes, E. coli SE5000 (pHP808), which carries the H. pylori urease gene cluster, was complemented with a lambda ZAP-derived plasmid library of the H. pylori chromosome. One of 1000 ampicillin-resistant clones, plated onto urea segregation agar, produced detectable urease. Urease activity of this co-transformant, grown in Luria broth containing 1 microM NiCl2, was 36 mumol NH3 min-1 mg-1 protein. Urease-enhancing activity, which is not directly linked to the urease gene cluster, was localized by subcloning and nucleotide sequencing. The largest open reading frame, designated nixA, predicted a polypeptide of 34,317 Da that displayed characteristics of an integral membrane protein. In vitro transcription-translation of nixA sequences yielded a polypeptide estimated to be 32 kDa in size. An in-frame Bal31 deletion within nixA abolished urease-enhancing activity. At 50 nM NiCl2, E. coli containing the nixA clone transported 1250 +/- 460 pmol Ni2+ min-1 10(-8) cells, whereas the vector control transported only 140 +/- 85 pmol Ni2+ min-1 10(8) cells, i.e. significantly less (P = 0.01). We conclude that NixA confers upon E. coli a high-affinity nickel-transport system (KT = 11.3 +/- 2.4 nM; Vmax = 1750 +/- 220 pmol Ni2+ min-1 10(-8) cells) and is necessary for expression of catalytically active urease, regardless of growth conditions.

Amino Acid Sequence↗

[Percutaneous endoscopic gastrostomy in long-term nutrition].

Percutaneous endoscopic gastrostomy is the preferred method for administration of long-term enteral tube feeding. Data on long-term follow-ups are rare. We report the long-term outcome and the complication rates after percutaneous endoscopic gastrostomy in 165 patients (mean age 70 years). The most common indications were neurologically-related swallowing disorders. The data were collected prospectively. Percutaneous endoscopic gastrostomy in patients was technically successful in 164 patients (99%), with a mean implantation time of 12 minutes. The procedure-related morbidity was 1.2%. The mean length of percutaneous endoscopic gastrostomy feeding was 26 weeks (1-98) for the Charrière 9-tube and 29 weeks (1-158) for Charrière 15-tubes. There were 12% tube-related and 15% feeding-related late complications, the main ones being local skin infections (7.3%) and gastric perforations (1.2%). The procedure-related mortality was 0.6%. We conclude that endoscopically assisted percutaneous gastrostomy is the procedure of choice for long-term enteral nutrition in patients requiring tube-feeding.

Adult↗

In vivo measurement of dye concentration using an evanescent-wave optical sensor.

A miniaturised evanescent-wave optical sensor is proposed for in vivo measurement of dye concentrations. It enables a continuous monitoring of the optical-dye attenuation or fluorescence spectra between 380 and 650 nm. The sensor is constructed with polished fibres: the cladding of a single-mode fibre is removed by longitudinal polishing. The proximity of the core to the medium favours penetration of the evanescent part of the modal field into the bio fluid. The dimensions of the probe permit several potential applications: for example, insertion into hypodermic needles for spectroscopic analysis of tissues and blood. In the paper, a gastro-enterologic application of the sensor introduced into a catheter is reported. In vivo tests demonstrate the feasibility of quantitative measurement of dye clearance in the gastro-oesophageal tract.

Coloring Agents↗

Cholecystokinin is a physiological regulator of gastric acid secretion in man.

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.

Adult↗