PubMed Health⌕ Search

Biomedical subjects

P Mortensen

Publications and source records attributed to P Mortensen.

16 recordsLinked to original sources
PubMed2001

Mass spectrometry allows direct identification of proteins in large genomes.

Proteome projects seek to provide systematic functional analysis of the genes uncovered by genome sequencing initiatives. Mass spectrometric protein identification is a key requirement in these studies but to date, database searching tools rely on the availability of protein sequences derived from full length cDNA, expressed sequence tags or predicted open reading frames (ORFs) from genomic sequences. We demonstrate here that proteins can be identified directly in large genomic databases using peptide sequence tags obtained by tandem mass spectrometry. On the background of vast amounts of noncoding DNA sequence, identified peptides localize coding sequences (exons) in a confined region of the genome, which contains the cognate gene. The approach does not require prior information about putative ORFs as predicted by computerized gene finding algorithms. The method scales to the complete human genome and allows identification, mapping, cloning and assistance in gene prediction of any protein for which minimal mass spectrometric information can be obtained. Several novel proteins from Arabidopsis thaliana and human have been discovered in this way.

Amino Acid Sequence↗
PubMed2001

Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure. A tissue doppler and three-dimensional echocardiographic study.

OBJECTIVES: We used tissue velocity imaging (TVI) and three-dimensional echocardiography to evaluate the effect of acute biventricular pacing on left ventricular (LV) performance and volumes in patients with severe heart failure and bundle branch block. BACKGROUND: Biventricular pacing causes acute hemodynamic improvement in patients with severe heart failure, and QRS duration has been used as a predictor of improved resynchronization. Tissue velocity has the potential of demonstrating the degree of LV resynchronization and three-dimensional echocardiography enables accurate quantitation of LV volumes and function. METHODS: TVI and three-dimensional echocardiography were performed during sinus rhythm and biventricular pacing in 25 consecutive patients with severe heart failure. RESULTS: Biventricular pacing significantly improved the extent of contracting myocardium in synchrony by 15.4% and the duration of contraction synchrony by 17% (p < 0.05 for both). Furthermore, end-diastolic and end-systolic volumes decreased by 7 +/- 4.5% and 13 +/- 6% (p < 0.01) and ejection fraction increased by 22.8 +/- 9% (p < 0.01). Baseline duration of QRS and the preejection period as well as the extent of myocardium with asynchronous contraction measured by TVI predicted pacing efficacy. In multivariate analysis, only the extent of myocardium with asynchronous contraction at the LV base predicted biventricular pacing efficacy. CONCLUSION: Biventricular pacing improves LV systolic performance and reduces LV volumes during short-term treatment. TVI provides important pathophysiological information on the degree of LV resynchronization and may contribute to improved patient selection.

Bundle-Branch Block↗
PubMed2000

Spectrophotometric and direct-reading methods for the analysis of gas phase peroxyacetic acid.

A new method for the determination of peroxyacetic acid (PAA) in gas phase samples is described. It is based on the oxidation of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate) by PAA with formation of a radical cation which is characterized by four strong absorption maxima between 405 nm and 810 nm. These allow for sensitive spectrophotometric determination of the peracid. The selectivity of the method towards hydrogen peroxide is strongly dependent on the sampling method used. Impinger sampling and sampling based on the use of coated solid sorbents (test tubes) was performed. Limits of detection are 10(-8) mol, limits of quantification are 5 x 10(-8) mol, the linear range consists of 1.5 concentration decades in both cases. Using ABTS-coated test tubes above 1 x 10(-7) mol, direct reading of the results is possible and may be used as rapid screening method for the PAA concentration.

Air Pollutants↗
PubMed2000

Determination of hydrogen peroxide in workplace air: interferences and method validation.

A dynamic system for the generation of stable hydrogen peroxide test atmospheres was applied to the evaluation of samplers used for the determination of hydrogen peroxide in workplace air. The system is able to generate gas mixtures of between 0.1 and 10 ppm at different combinations of relative humidity (20-80%) and temperature (10-30 degrees C). Gaseous hydrogen peroxide is sampled on glass filters impregnated with Ti(IV) chloride and sulfuric acid and analyzed by UV spectroscopy. An interference was observed due to the acid catalyzed decomposition of peroxyacetic acid to hydrogen peroxide. This was significantly reduced by applying high sample flow rates and by lowering the concentration of sulfuric acid. The performance of the sampler and sources of uncertainties were tested according to the European Standard EN 1076.

Air Pollution, Indoor↗
PubMed2000

Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia.

AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose-response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females.

Adolescent↗
PubMed1999

Determination of gas phase peroxyacetic acid using pre-column derivatization with organic sulfide reagents and liquid chromatography.

The first selective HPLC methods for the determination of peroxyacetic acid (PAA) in gas phase samples have been developed. PAA reacts with 2-([3-{2-[4-amino-2-(methylsulfanyl)phenyl]- 1-diazenyl}phenyl]sulfonyl)-1-ethanol (ADS) to form the corresponding sulfoxide. Sampling may be performed in impingers using aqueous solutions of the reagent or by test tubes with the reagent coated on a solid sorbent. Sulfide and sulfoxide are separated by means of HPLC and detected at a wavelength of 410 nm. The method is highly selective for PAA in the presence of hydrogen peroxide when sampling in impingers. A 10,000-fold excess of hydrogen peroxide leads to the same peak area compared to PAA. Limit of detection is 10(-8) mol PAA, thus corresponding to PAA concentration of 46 ppb when using a sampling time of 10 min with a flow-rate at 500 ml/min. Another sulfide reagent, methyl-p-tolyl sulfide (MTS) has been used in a similar way with impinger sampling. Major advantages of ADS towards MTS are improved UV-Vis spectroscopic properties and reduced volatility.

Chromatography, High Pressure Liquid↗
PubMed1999

The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study.

In conjunction with pharmacologic therapy, pacing has been proposed as a potential treatment to decrease symptoms in patients with moderate-to-severe congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF dealing with different pacing sites, modes of pacing, and atrioventricular delays have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial designed to evaluate the effects of pacing on acute hemodynamic function and to assess chronic clinical benefit in patients with moderate-to-severe CHF. The effect of pacing on oxygen consumption at peak exercise and at anaerobic threshold during cardiopulmonary exercise tests, and on 6-minute walk distance, have been selected as primary endpoints of the study. Secondary endpoints of the trial were changes in New York Heart Association (NYHA) functional class, quality-of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and hospitalization frequency. Finally, changes in ejection fraction, cardiac output, and filling pattern were assessed by echocardiography. The trial was planned to include 53 patients from 7 centers in Europe over a period of 3 years. The study was divided into 2 parts: acute testing and chronic follow-up. The acute study, performed during the pacemaker implantation, involved extensive testing using a custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM protocol) to determine the best ventricular pacing sites and the most appropriate atrioventricular delays. The chronic phase consisted of a crossover study designed to test in each patient the best univentricular pacing site and biventricular pacing as assessed by the acute hemodynamic study. The study started with the first implant in 1995 and has, to date, included 42 patients. The study is expected to be completed by the end of 1998. The results of a first interim analysis showed trends toward improvement in all primary and secondary endpoints during the pacing periods compared with no pacing.

Adult↗
PubMed1999

A randomized controlled clinical trial comparing ventricular fibrillation detection time between two transvenous defibrillator models. The Acute Ventak AV investigator group.

The Ventak AV is an implantable cardioverter defibrillator with dual chamber pacing capability. Features include detection and treatment of ventricular arrhythmias, detection of atrial arrhythmias, as well as dual chamber pacing. The objective of the investigation was to verify the efficacy of the Ventak AV in detecting ventricular fibrillation in the presence of dual chamber pacing. Thirty-three patients, who were to receive an implantable defibrillator were randomized (1:1) in a paired comparison study to the Ventak AV (study device) and the Ventak Mini (control) during defibrillation threshold testing. In order to create a "worst case scenario" for sensing of ventricular fibrillation, pacing was performed at high lower rate limit values (Ventak AV DDD pacing at 150/min, Ventak Mini at VVI 100/min). Ventricularfibrillation was induced and the randomized device was allowed to detect and treat the arrhythmia. This test was repeated for each patient using the alternate device in a randomized order, such that all patients were tested with both devices. The mean ventricular fibrillation detection time for the Ventak AV was 2.0+/-0.11 seconds and for the control device the detection time was 1.8+/-0.11 seconds (P = 0.26). Appropriate tachyarrhythmia therapy decision was documented in all episodes for both devices. The study patient population demonstrated equivalent ventricular fibrillation detection time between the Ventak AV and the Ventak Mini. The Ventak AV demonstrated effectiveness in detecting ventricular fibrillation in the presence of high rate dual chamber pacing.

Adult↗
PubMed1997

[Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology].

The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.

Anesthesiology↗
PubMed1997

Automation of matrix-assisted laser desorption/ionization mass spectrometry using fuzzy logic feedback control.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is a sensitive and versatile method for biomolecular analysis which has potential for high-throughput screening in many applications. To obtain mass spectra of optimal quality, however, laser fluence is continuously adjusted during data acquisition to be close to the threshold level of ion production, requiring a skilled operator and several minutes of acquisition time per sample. Using real-time fuzzy logic control of the laser fluence, we here demonstrate that the acquisition of MALDI spectra can be automated without reduction of data quality. The control algorithm evaluates signal intensity and mass resolution of the base peak. It then regulates the laser fluence to keep the ion signal intensity within the dynamic range of the data acquisition hardware while maintaining high mass resolution. This fuzzy logic control system allows unattended data acquisition using either static ion extraction or delayed ion extraction MALDI. Even for difficult samples such as femtomole-level peptide mixtures, no significant reduction in data quality is observed, as compared to manually obtained spectra. Automated analysis of 78 chromatographic fractions with high mass accuracy demonstrates the utility of the method. The control algorithm has been combined with other software modules to completely automate database identification of proteins by their peptide mass maps. The success of fuzzy logic in MALDI automation suggests wider uses of this technique in mass spectrometry.

Automation↗
PubMed1996

Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels.

The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an example, we demonstrate here that mass spectrometric protein identification is a general solution to this problem given a completely sequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mixtures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectrospray tandem mass spectrometry followed by data base searching with multiple peptide sequence tags. In blind trials, the method led to unambiguous identification in all cases. In the largest individual protein identification project to date, a total of 150 gel spots-many of them at subpicomole amounts-were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1995

Absence of correlation between hepatic function and characteristics of migrating motor complexes in the gastrointestinal tract.

BACKGROUND: Cyclic changes in gallbladder filling and emptying during the migrating motor complex (MMC) cycle have been demonstrated by scintigraphy. However, a possible cyclic change in the hepatic function and handling of the pharmacologic agents used for scintigraphy during the MMC cycle could have an influence on these results. The aim of the present study was to investigate the hepatic handling of cholic acid and mebrofenin in relation to the MMCs of the gastrointestinal tract. METHODS: The plasma disappearance rate of 14C-cholic acid and the hepatic uptake and excretion of 99mTc-mebrofenin were examined during phase I and phase II of the MMC in six healthy male volunteers. RESULTS: The plasma disappearance rate of 14C-cholic acid showed a biexponential course with an initial rapid and late slow phase after a bolus injection. There were no significant differences between the initial or late plasma disappearance rate of 14C-cholic acid during phase I as compared with phase II. The results of the time-activity curves from the 99mTc-mebrofenin scintigraphy showed an exponential rapid increase in radioactivity followed by an almost linear slow decrease after a bolus injection. There was no significant difference between phase I and phase II in any of the variables studied. CONCLUSION: The lack of a relationship between hepatic handling of cholic acid and mebrofenin and MMC excludes this as a possible source of error in the investigations of the dynamic function of the enterohepatic circulation and especially gallbladder motility by the use of either cholic acids or iminodiacetic acid derivatives as investigative agents.

Adult↗
PubMed1992

Nonpharmacologic treatment of supraventricular and ventricular tachyarrhythmias. A review of 249 consecutive patients.

Incapacitating or life-threatening tachyarrhythmias were treated nonpharmacologically in 249 patients from 1982 to 1991. Among 92 patients surgically treated for supraventricular tachycardia the cure rate was 93% and the complication rate 12%. Radiofrequency catheter ablation gave an equal cure rate in 51 patients, but with no major complications or mortality. Direct-current catheter ablation of the His bundle was successful in 96% of 27 patients with drug-refractory atrial fibrillation or other supraventricular tachyarrhythmias. Among 64 patients undergoing surgery for ventricular tachycardia/ventricular fibrillation, the perioperative mortality was 9%, estimated 5-year survival 69% and estimated 5-year freedom from the preoperative arrhythmias 72%. Of 18 patients treated with implantable cardioverter defibrillator, three (18%) died of heart failure during follow-up. Nonpharmacologic treatment of tachyarrhythmias is concluded to be effective and often definitively curative. The safety-risk ratio is improving as new treatment modalities are developed.

Adolescent↗
PubMedDate not supplied

Acute appendicitis and plasma concentration of serotonin.

The concentration of serotonin in platelet-poor plasma was measured with a radioenzymatic method in 31 patients prior to operation for suspected acute appendicitis. The serotonin determinations were made without knowledge of the peroperative or histologic findings. Appendicitis was found in 20 patients, nine of whom had elevated plasma serotonin level, giving 45% sensitivity for the test. Of the 11 patients with normal appendix, only one had increased plasma serotonin, giving 91% specificity. The predictive value of normal serotonin level was 48% and that of elevated serotonin level was 90%. No correlation was found between duration of appendicitis symptoms and plasma serotonin concentration. Other diseases did not influence the serotonin level.

Acute Disease↗