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Biomedical subjects

M De Pauw

Publications and source records attributed to M De Pauw.

At least 19 recordsLinked to original sources
PubMed2004

Role of force--frequency relation during AV-block, sinus node block and beta-adrenoceptor block in conscious animals.

OBJECTIVE: Myocardial contractility is regulated by adrenergic stimulation, the strength-length relationship and the force-frequency relationship or Bowditch effect. The latter mechanism was clearly demonstrated in muscle strips, in the isolated heart as well as in in-vivo experiments. The aim of this study was to further investigate the role of the force-frequency effect on the contractile response to exercise or isoproterenol infusion in conditions of restricted increases in heart rate i.e., AV-block, sinus node block and beta-adrenoceptor block. METHODS: Nineteen dogs were instrumented with a left ventricular miniature pressure gauge, catheters in the aorta, pulmonary artery and left atrium and pacing leads on the left atrium and left ventricle. In order to control the chronotropic response during sympathetic stimulation, permanent AV-block was induced in nine dogs, sinus node block using UL-FS 49 and beta-adrenoceptor block using propranolol was studied in ten dogs. RESULTS: Adrenergic stimulation (isoproterenol 0.4 micro g/kg or exercise) after total AV-block failed to increase LVdP/dt. However, increasing LV pacing rate (from 50 up to 200 bpm) prior to adrenergic stimulation elicited a significant increase in LVdP/dt (4762 +/- 166 mmHg/s vs. 6485 +/- 381 mmHg/s, p < 0.05). In dogs in sinus rhythm, heart rate and LVdP/dt response to isoproterenol and exercise following pre-treatment with UL-FS 49 is significantly reduced, with heart rate increasing from 103 +/- 7 up to 154 +/- 5 bpm and LV dP/dt(max) from 2925 +/- 171 mmHg/s to 6249 +/- 400 mmHg/s compared to the response in control conditions (HR 220 +/- 3 bpm and LV dP/dt(max) 7473 +/- 616 mmHg/s) (p < 0.05). When heart rate is matched using atrial pacing, the LVdP/dt(max) response reached comparable values as observed in control conditions (7310 +/- 550 mmHg/s). Similar responses were obtained during exercise. Beta-adrenoceptor blockade attenuates considerably the heart rate and LVdP/dt response to sympathetic stimulation. Adjusting heart rate with atrial pacing restores only partially LVdP/dt(max). CONCLUSION: During sympathetic stimulation, the chronotropic response plays a major role for the concomitant full expression of the inotropic response. In conditions where increases in heart rate are absent or severely restricted such as in permanent AV-block, sinus node block and beta-adrenoceptor block, the inotropic response will also be impaired.

Adrenergic beta-Agonists↗
PubMed2002

Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation.

BACKGROUND: There is a need for better tolerated drugs to normalize bowel function in chronic constipation. Prucalopride is a highly selective, specific, serotonin4 receptor agonist with enterokinetic properties. AIM: To evaluate the effects of prucalopride on bowel function, colonic transit and anorectal function in patients with chronic constipation. METHODS: Twenty-eight patients were enrolled in this double-blind, placebo-controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16). Patients kept a bowel function diary. Colonic transit times and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed. RESULTS: Prucalopride (1 mg) compared to placebo significantly increased the mean number of spontaneous complete, spontaneous and all bowel movements per week. Prucalopride (1 mg) significantly decreased the percentage of bowel movements with hard/lumpy stools and straining and increased the urge to defecate. Prucalopride (1 and 2 mg) decreased the mean total colonic transit time by 12.0 h (prucalopride 42.8 h vs. placebo 54.8 h; P=0.074). No statistically significant effects were found in any of the anorectal function parameters. Prucalopride was well tolerated. There were no clinically relevant changes in standard safety parameters. CONCLUSIONS: Prucalopride significantly improves stool frequency and consistency, and the urge to defecate, and may decrease colonic transit times in patients with chronic constipation.

Adolescent↗
PubMed2002

Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury.

BACKGROUND: Chronic constipation (CC) often occurs after spinal cord injury (SCI). Prucalopride is a novel, highly selective, specific serotonin4 receptor agonist with enterokinetic properties. We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCL. METHODS: Double-blind, placebo-controlled, pilot, phase 11, dose-escalation study. After 4 weeks' run in, patients received prucalopride 1 mg (n = 8) or placebo (n = 4); 11 new patients were randomized to prucalopride 2 mg (n = 8) or placebo (n = 3) once daily for 4 weeks. Patients recorded bowel function (diary) and assessed constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100 mm). Colonic transit times were determined. RESULTS: Compared with run in. mean changes in constipation severity (VAS) increased with placebo, but decreased with prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data showed an improvement in average weekly frequency of all bowel movements over 4 weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a significant reduction in median colonic transit time with 2 mg (n = 4; -38.5 h (95% CI -80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain, and two of these discontinued treatment. There were no clinically relevant effects on any of the safety parameters. CONCLUSION: This pilot study indicates that prucalopride can play an important role in the management of patients with CC due to SCI.

Adolescent↗
PubMed2001

Preinfarction angina protects against out-of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery.

OBJECTIVES: The goal of this study was to evaluate the effect of preconditioning on out-of-hospital ventricular fibrillation (VF) in patients with acute myocardial infarction (AMI). BACKGROUND: More than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. In humans, preinfarction angina (PA), which can serve as a surrogate marker for preconditioning, reduces infarct size, but the protective effect against out-of-hospital VF has not been investigated. METHODS: Preinfarction angina status and acute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with 144 matched controls without this complication. RESULTS: Preinfarction angina is associated with a lower risk for VF (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.18 to 0.88). In patients with acute occlusion of the left coronary artery (LCA) (n = 136), the risk reduction is pronounced (OR: 0.25, 95% CI: 0.10 to 0.66), whereas, in patients with acute occlusion of the right coronary artery (RCA) (n = 67), the protective effect of PA on VF was not observed (OR: 2.25, 95% CI: 0.45 to 11.22). Subgroup and multivariate analyses show that the protective effect is independent of cardiovascular risk factors, preinfarction treatment with beta-adrenergic blocking agents or aspirin, the presence of collaterals or residual antegrade flow or the extent of coronary artery disease. CONCLUSIONS: Preinfarction angina protects against out-of-hospital VF in patients with acute occlusion of the LCA. This protection is independent of risk factors or coronary anatomy. A larger study is needed to examine the apparently different effect in patients with acute occlusion of the RCA.

Adrenergic beta-Antagonists↗
PubMed2001

Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction.

BACKGROUND: In acute myocardial infarction (AMI) treated conservatively or with thrombolysis, marked increases of C-reactive protein (CRP) and fibrinogen have been observed. No data are however available concerning a possible relation between CRP and fibrinogen levels on admission and markers of infarct size after obtaining thrombolysis in myocardial infarction (TIMI) flow III by primary angioplasty. METHODS: We studied 34 patients with a first AMI (29 men, mean age 54+/-11 years) who were treated with primary angioplasty (TIMI flow III in all patients, no concomitant treatment with glycoprotein IIb-IIIa antagonists) within 6 h of onset of pain. CRP and fibrinogen levels on admission were determined and related to the following markers of infarct size: peak creatine kinase MB (CKMB) levels, radionuclide left ventricular ejection fraction (LVEF) at discharge and thallium-201 single-photon emission computed tomography (SPECT) infarct size at 1 month. RESULTS: Median CRP levels were 0.4 mg/dl (range 0.09-3 mg/dl), median fibrinogen levels 412 mg/dl (range 198-679 mg/dl), mean CKMB was 178+/-151 U/l, mean LVEF 52+/-8% and mean thallium-201 infarct size 7+/-6%. Although CRP levels were related to fibrinogen levels on admission (r=0.56, P=0.002), only fibrinogen levels were related to markers of infarct size (r=0.58, P=0.001 for CKMB, r=-0.44, P=0.01 for LVEF and r=0.64, P=0.001 for thallium-201 infarct size). No relation was found between CRP or fibrinogen levels on admission and the extent of coronary artery disease or the myocardial area at risk. In multiple regression analysis, the relation between fibrinogen and markers of infarct size was independent of CRP levels and the duration of pain on admission. CONCLUSIONS: These findings indicate a relation between fibrinogen levels on admission and myocardial infarct size in patients treated with primary angioplasty for AMI. This relation seems to be independent of CRP levels and the duration of pain on admission. If confirmed in larger patient populations, fibrinogen levels on admission could have an important value for risk stratification and more aggressive reduction of infarct size in patients who are treated with primary angioplasty.

Acute Disease↗
PubMed2001

Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja.

A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI(50), 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).

Alkaloids↗
PubMed2001

Redo mitral surgery using the Estech endoclamp.

BACKGROUND: Redo-CABG surgery remains extremely hazardous in the presence of open bypass grafts. In our patients with mitral valve pathology with open and well-functioning bypass grafts, we explored alternative approaches in order to avoid damage to the grafts by extensive dissection and direct clamping of the ascending aorta. The "Estech procedure," which uses the Estech remote access perfusion (RAP) endoclamp catheter (Estech Inc., Danville, CA), was selected for these patients. METHODS: From January 1998 to January 2000, 10 patients underwent an Estech procedure for redo mitral surgery. All patients had previous cardiac operations such as coronary artery bypass grafting (CABG) and/or mitral valve procedures. The Estech procedure consisted of an anterior left thoracotomy and peripheral cannulation at femoral site using the Estech endovascular balloon technique. The series was comprised of seven mitral valve replacements, two valve reconstructions, and one closure of a paravalvular leak. One procedure had to be converted to a standard re-sternotomy due to extreme arteriosclerosis of the descending aorta with plaque dislocation at the time of catheter insertion. However, no damage was inflicted to the open bypass grafts. RESULTS: The follow-up period ranged from six to 30 months and was 100% complete. We encountered one hospital death in our group, which was due to a late post-operative intestinal infarction and multiple organ failure (MOF), and was not procedure related. As expected, morbidity was high in this compromised cohort, but no late death has occurred prior to submission of this article. All survivors progressed to an acceptable NYHA functional class. CONCLUSION: The excellent results in this complex patient group inspired us to use the Estech procedure as a standard approach for redo mitral surgery.

Coronary Artery Bypass↗
PubMed2000

Diagnosis of a coronary artery fistula thirty years after myectomy for septal hypertrophy.

A 61-year-old asymptomatic male patient was evaluated before abdominal surgery. He has a history of septal myectomy in 1969 and an episode of atrial flutter in 1983. On auscultation an atypical murmur was heard. By transthoracic echocardiography the diagnosis was made of a coronary artery fistula after septal myectomy. We discuss the prevalence, diagnosis and natural history of coronary artery fistulas. In our patient we followed a conservative strategy.

Cardiac Surgical Procedures↗
PubMed1999

Incessant automatic atrial tachycardia: a reversible cause of tachycardiomyopathy.

We describe the case of a 23-year-old man with incessant atrial tachycardia complicated with tachycardiomyopathy. Transseptal ablation of the arrhythmia focus, located between the ostia of the left and right inferior vena pulmonalis, resulted in a restoration of normal sinus rhythm and a complete regression of the signs of tachycardiomyopathy.

Adult↗
PubMed1997

Composition and structural and functional properties of discoidal and spherical phospholipid-apoE3 complexes.

To model the common structural unit in the system of reverse cholesterol transport, we studied the composition, structure, and physicochemical properties of complexes generated between dipalmitoylphosphatidylcholine (DPPC) or palmitoyllinoleoylphosphatidylcholine (PLPC) and apoE3 in the absence and in the presence of cholesterol (Chol); the data were compared with similar experiments using apoA-I, the major proteins of high-density lipoproteins. The conformation and organization of lipid-binding domains of apoE3 within the complexes were calculated by computer modeling. The transition temperatures of DPPC within discoidal complexes with mean diameters of 116 A (GGE) or 148 A (EM) were higher for complexes versus liposomes both in the absence and in the presence of Chol. Association of apoE3 with DPPC resulted in a more structured state of the apolipoprotein molecule versus the soluble apolipoprotein; this state was characterized by parallel orientation of alpha-helixes of apoE3 and DPPC acyl chains. Substrate efficiency of the apoE3-PLPC-Chol complexes in the lecithin-cholesterol acyltransferase (LCAT) reaction expressed as Vmax/Km was 0.5 mole cholesteryl esters/h per 1 microM. The transformation of discoidal apoE3-DPPC-Chol complexes into spherical particles was induced by LCAT and accumulation of cholesteryl esters was approximately 62% of the total cholesterol. Parallel orientation of phospholipid acyl chains with helical segments disappeared in these particles. Discoidal apoE3-DPPC complexes incorporated unesterified cholesterol released from Chol-loaded J774 macrophages. The data support the concept that association of apoE3 and apoA-I with phospholipids is qualitatively similar due to similar orientation of helical repeats in the C-terminal domains of apoE3 and apoA-I.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Comparison of lipid-binding and lecithin:cholesterol acyltransferase activation of the amino- and carboxyl-terminal domains of human apolipoprotein E3.

To extend the characterization of the functional domains of apolipoprotein E (apoE), the amino-(residues 1-191, 22-kDa) and carboxyl-terminal (residues 216-299, 10-kDa) fragments were tested for lipid binding and lecithin:cholesterol acyltransferase (LCAT) activation. A disulfide bond linking helices 2 and 3 of the four-helix bundle amino-terminal domain was introduced by mutating threonine-57 to cysteine (Thr57-->Cys) in apoE3 (cysteine at position 112) to determine the influence of the disulfide bond on the properties of this domain. Lipid-binding properties were determined by the ability to form complexes with dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine, assessed by measuring decreases in turbidity as a function of temperature. The results demonstrate that the relative lipid binding efficiencies were intact apoE3 approximately 10-kDa fragment > 22-kDa fragment > Thr57-->Cys variant. In addition, free, non-lipid-associated protein was observed with the two 22-kDa fragments but not with intact apoE3 or the 10-kDa fragment. The transition temperatures determined by fluorescence polarization were higher for the DMPC complexes with intact apoE3 and with 22- and 10-kDa fragments (25.5 degrees C) than with the 22-kDa Thr57-->Cys variant (23.5 degrees C), suggesting that the variant fragment possessed the lowest affinity for lipid. Attenuated total reflection infrared measurements of the complexes indicated that the long axes of the alpha-helices of the various apoE forms were parallel to the acyl chains of the phospholipid bilayer.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein E3↗
PubMed1995

Helix-helix interactions in reconstituted high-density lipoproteins.

In this work we calculated the ionic interactions between adjacent amphipathic helices of apo A-I and apo A-IV. The calculation of the electrostatic potential around the helices helps identify the charged residues susceptible to form salt bridges between adjacent helices. An estimation of the stability of the different pairs of helices is derived from the calculation of the energy of interaction between contiguous helices at a water/lipid interface after energy minimization. The most stable energetic conformation corresponds to the 17-residue helices oriented anti-parallel and separated by a stretch of 5 residues in an extended beta-strand conformation, as calculated through the 'stereo alphabet' calculation procedure. In a pair of helices, the hydrophobic faces are directed towards the lipid core of the discoidal phospholipid-apolipoprotein complex and the hydrophobic lipid-protein interactions are major determinants for the stability of the complex. Interactions between polar residues located on the opposite face of the helix and water molecules can also contribute to the overall energy of the system. Finally, salt bridge formation between residues of opposite charge along the edge of the helical segments contribute to the cooperativity of the phospholipid-apolipoprotein complex formation. The mode of assembly of the amphipathic helical repeats of the apolipoproteins around the edge of a discoidal complex is therefore determined both by the hydrophobic character of the residues and by the charge complementarity along the edge of the helices which increases the structural stability and determines the relative orientation of the helices.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group.

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

Administration, Oral↗
PubMed1995

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of 2 European Organization for Research and Treatment of Cancer randomized trials with mitomycin C and doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment. European Organization for Research and Treatment of Cancer Genitourinary Group.

The European Organization for Research and Treatment of Cancer genitourinary group has completed 2 parallel prospective randomized studies, one with 30 mg. mitomycin C and the other with 50 mg. doxorubicin as adjuvant intravesical treatment after transurethral resection of superficial transitional cell bladder carcinoma. These studies were designed to compare early (the day of resection) versus delayed (between 7 and 15 days after resection) instillations and short-term (6 months) versus long-term (12 months) treatment. The results indicate that in regard to recurrence rate patients having a delayed and short-term treatment do worse than those having early instillations (for 6 or 12 months) or those having prolonged treatment (either immediate or delayed). With an average followup of 4 years survival, progression beyond T1 disease, development of distant metastases and appearance of a second primary were not influenced by the therapeutic regimen. A multivariate analysis of prognostic factors is presented, which indicates that after adjustment for these factors, patients in the delay, no maintenance arm have a significantly higher recurrence rate than the other patients.

Administration, Intravesical↗
PubMed1994

Apolipoprotein E self-association in solution studied by non-radiative energy transfer.

The self-association of human apolipoprotein E (apoE), isolated from plasma very low density lipoproteins, was studied at apoE concentrations less than 0.6 microM by non-radiative energy transfer. ApoE was separately labeled with a fluorescent donor group i.e. dansyl chloride (apoE/D) and with an acceptor i.e. fluorescein isothiocyanate (apoE/F). Mixed apoE/D:apoE/F complexes were prepared either by incubation or the donor- and of the acceptor-labeled apoE or by renaturation during dialysis of the apoE/D:apoE/F mixture pre-denatured by addition of guanidine hydrochloride or by treatment with sodium cholate. The efficiency of energy transfer E at an equimolar ratio of the donor to acceptor and a ratio of 1.9 mol fluorescein/mol protein amounted to 29.2 +/- 2.6% (n = 3). The E value increased linearly with increasing acceptor fraction in the mixture. The state of self-association of apoE as tetramers within this concentration range was confirmed by cross-linking experiments with a water-soluble bifunctional reagent. This approach can be applied to the study of protein-protein interactions in apolipoprotein-phospholipid recombinants.

Apolipoproteins E↗
PubMed1994

Quality control in data monitoring of clinical trials.

Eligibility of a patient is based on the patient's status at the time of registration/randomization in the trial and not on something that happens to the patient after entry in the study. All patients entered must be included in the statistical analyses and accounted for in the publication of the results. Stratification done at the time of randomization is used to avoid major imbalances with respect to the distribution of prognostic factors in the different treatment groups. This goal is accomplished only if the information given at randomization is accurate. For this reason, all information given at randomization should be recorded and inserted in the patient's medical file and the randomization done as close as possible to the start of treatment. Protocol violations are to be anticipated but must be kept as low as possible because their percentage will reflect on the quality of the trial. Patients lost to follow up must be kept to a minimum. If patients can no longer attend the consultations at the frequency described in the protocol, every attempt should still be made to follow them for survival. Finally, a clinical trial should be conducted in the time interval foreseen to maintain interest and patient recruitment.

Clinical Protocols↗