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Biomedical subjects

R J Peters

Publications and source records attributed to R J Peters.

At least 37 records · Page 2Linked to original sources
PubMed2000

Videodensitometric quantitative angiography after coronary balloon angioplasty, compared to edge-detection quantitative angiography and intracoronary ultrasound imaging.

AIMS: To assess the value of videodensitometric quantification of the coronary lumen after angioplasty by comparison to two other techniques of coronary artery lumen quantification. METHODS AND RESULTS: Videodensitometric quantitative angiography, edge detection quantitative angiography and 30 MHz intracoronary ultrasound imaging were performed after successful balloon angioplasty in 161 patients. Lumen cross-sectional areas were mean (SD) 2.82 (1.15) mm(2)for edge detection quantitative angiography, 3.67 (1.5) mm(2)for videodensitometric quantitative angiography and 5.32 (1.75) mm(2)for intracoronary ultrasound imaging (P<0.001). The correlation between intracoronary ultrasound imaging and videodensitometric quantitative angiography (r=0.44) was almost similar to that of intracoronary ultrasound imaging and edge detection quantitative angiography (r=0. 47). The correlation between the three techniques was not significantly influenced by the presence of ruptures and dissections on intracoronary ultrasound imaging. The absence of calcifications improved the correlation between videodensitometry and intracoronary ultrasound imaging. CONCLUSIONS: The luminal dimensions as measured by videodensitometric quantitative angiography matched intracoronary ultrasound imaging derived dimensions more closely than edge detection quantitative angiography. Videodensitometric quantitative angiography represents an on-line alternative to intracoronary ultrasound imaging for quantitative analysis regardless of the degree of vessel damage.

Absorptiometry, Photon↗
PubMed2000

Activation of clotting factors XI and IX in patients with acute myocardial infarction.

In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.

Angina Pectoris↗
PubMed2000

Successful attenuation of venous thrombus growth in rabbits after the administration of a novel oral thrombin inhibitor.

Current antithrombotic compounds have several limitations in clinical practice. The present study was designed to investigate a novel orally available direct thrombin inhibitor, BSF 208791. Intravenous administration of BSF 208791 showed superior antithrombotic properties as compared with Polyethylenglycol-Hirudin (PEG-Hirudin) and low molecular weight heparin (LMWH) in a model of venous thrombosis in rabbits. The thrombus growth was 22%, 30%, 37% and 50% after BSF 208791, PEG-Hirudin. LMWH, and saline administration, respectively. Moreover, bleeding time was less affected after administration of BSF 208791 as compared with PEG-Hirudin. The oral administration of BSF 208791 resulted in adequate bioavailability and significantly reduced venous thrombus growth to 36% as compared with 60% in the saline treated rabbits. The antithrombotic effect of BSF 208791 appears to be superior to PEG-Hiridin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombotic therapy.

Administration, Oral↗
PubMed1999

[Thrombocyte receptors: current views and therapeutic options].

In the action of thrombocytes during stemming of a bleeding after damage to a blood vessel, receptors on the thrombocyte membrane play an important part. Adhesion of platelets takes place via specific binding of receptors; the main binding is that of glycoprotein (Gp) Ib to Von Willebrand factor which is synthetized by endothelial cells. Activation of thrombocytes is stimulated by adhesion and by agonists. Weak agonists, through production of thromboxane A2 and release of agonists from granules cause a self-fortifying process of thrombocyte stimulation; strong agonists (like thrombin) lead also to activation of Gp IIb/IIIa receptors. Aggregation of thrombocytes occurs after activation of Gp IIb/IIIa receptors. During stimulation, a change of shape occurs which enables binding to suitable plasma proteins of which the main one is fibrinogen. Knowledge of thrombocyte receptors enhances the insight into the prognosis and efficacy of certain treatments in diseases in which platelet aggregation is pivotal. Of the six categories of antiplatelet drugs, antagonists of Gp IIb/IIIa receptors are the most potent. In clinical trials good results have been obtained in patients with coronary disease of the intravenously administered form added to acetylsalicylic acid.

Blood Platelets↗
PubMed1999

alpha-lytic protease precursor: characterization of a structured folding intermediate.

The bacterial alpha-lytic protease (alphaLP) is synthesized as a precursor containing a large N-terminal pro region (Pro) transiently required for correct folding of the protease [Silen, J. L., and Agard, D. A. (1989) Nature 341, 462-464]. Upon folding, the precursor is autocatalyticly cleaved to yield a tight-binding inhibitory complex of the pro region and the fully folded protease (Pro/alphaLP). An in vitro purification and refolding protocol has been developed for production of the disulfide-bonded precursor. A combination of spectroscopic approaches have been used to compare the structure and stability of the precursor with either the Pro/alphaLP complex or isolated Pro. The precursor and complex have significant similarities in secondary structure but some differences in tertiary structure, as well as a dramatic difference in stability. Correlations with isolated Pro suggest that the pro region part of the precursor is fully folded and acts to stabilize and structure the alphaLP region. Precursor folding is shown to be biphasic with the fast phase matching the rate of pro region folding. Further, the rate-limiting step in oxidative folding is formation of the disulfide bonds and autocatalytic processing occurs rapidly thereafter. These studies suggests a model in which the pro region folds first and catalyzes folding of the protease domain, forming the active site and finally causing autocatalytic cleavage of the bond separating pro region and protease. This last processing step is critical as it allows the protease N-terminus to rearrange, providing the majority of net stabilization of the product Pro/alphaLP complex.

Circular Dichroism↗
PubMed1999

Hyperemic coronary flow after optimized intravascular ultrasound-guided balloon angioplasty and stent implantation.

OBJECTIVES: This study evaluated the acute physiological gain of adjunctive intravascular ultrasound (IVUS) guided balloon angioplasty and stent implantation. BACKGROUND: Recent studies indicate safe coronary luminal enlargement and "stent-like" long-term outcomes using upsized balloons guided by IVUS. METHODS: After angiographically guided balloon angioplasty in 20 patients with 1-vessel disease and normal left ventricular function, IVUS was performed to determine the size of the adjunctive balloon using the mean of the maximal luminal diameter and the maximal diameter of the external elastic membrane measured in the adjacent proximal and distal reference segments. Serial adenosine-induced hyperemic blood flow velocity measurements were performed using a 0.014" Doppler guide wire to determine the physiological lumen obstruction after standard balloon angioplasty, followed by IVUS-guided balloon angioplasty and stent implantation. RESULTS: Upsized balloon angioplasty (increase balloon size: 0.98 +/- 0.26 mm; balloon:artery ratio 1.35 +/- 0.21) resulted in an additional increase of arterial dimensions: minimal lumen diameter (MLD) 2.18 +/- 0.38 mm to 2.73 +/- 0.51 mm; percent diameter stenosis (%DS) 34 +/- 13% to 19 +/- 22%; IVUS assessed minimal lumen area (MLA) 7.53 +/- 1.55 mm2 to 10.24 +/- 2.22 mm2 (all p < 0.0001). Major dissections (> or = type C) did not occur. Hyperemic blood flow velocity increased from 49.8 +/- 20.1 cm/s to 59.1 +/- 22.9 cm/s (p < 0.05) after IVUS-guided balloon angioplasty. Adjunctive stent implantation resulted in a further increase of MLD to 3.84 +/- 0.51 mm, %DS to -9 +/- 21% and MLA to 13.39 +/- 1.80 mm2 (all p < 0.0001), while hyperemic blood flow velocity remained unchanged (61.2 +/- 24.7 cm/s, p = 0.7). CONCLUSIONS: Upsized IVUS-guided balloon angioplasty increases arterial coronary dimensions and the distal hyperemic blood flow velocity. Adjunctive stent implantation does not yield a further gain in the hyperemic blood flow velocity, indicating the absence of a functional residual lumen obstruction after IVUS-guided balloon angioplasty. This may explain a similar clinical outcome reported after those coronary interventions.

Adult↗
PubMed1999

Ruling out acute myocardial infarction early with two serial creatine kinase-MBmass determinations.

AIMS: We studied the diagnostic value for acute myocardial infarction of serial creatine kinase-MBmass measurements on admission and at 7 h after the onset of symptoms. METHODS AND RESULTS: Patients presenting to our chest pain unit with symptoms of <5-h duration were eligible. Patients were kept under observation at least until 12 h after onset of symptoms. Blood samples were drawn on admission and 7 and 10 h after onset of symptoms. Creatine kinase-MBmass>7.0 microg x 1(-1) (upper reference limit for acute myocardial infarction), or an increase >2.0 microg x 1(-1) (reference change value) between admission and at 7 h was considered abnormal. Of a total of 470 patients, 248 patients had acute myocardial infarction: 100 out of the 248 patients had a single creatine kinase-MBmass>7.0 microg x 1(-1) on admission (sensitivity 40%, 95% CI:34-46%), 234/248 patients at 7 h (sensitivity 94%, 95% CI:91-97%), and 240/248 at 10 h (sensitivity 97%, 95% CI:94-99%). At 7 h, 246/248 patients had either a single creatine kinase-MB >7.0 microg x 1(-1) or a significant increase between admission and 7 h (sensitivity 99%, 95% CI:98-100%). Of 222 patients without acute myocardial infarction, 214 had a normal serial creatine kinase-MBmass (specificity 96%, 95% CI:93-98%). CONCLUSION: In patients with symptoms of <5-h duration, acute myocardial infarction can be ruled out using serial creatine kinase-MBmass taken on admission and at 7 h.

Adult↗
PubMed1998

Pro region C-terminus:protease active site interactions are critical in catalyzing the folding of alpha-lytic protease.

alpha-Lytic protease is encoded with a large (166 amino acid) N-terminal pro region that is required transiently both in vivo and in vitro for the correct folding of the protease domain [Silen, J. L. , and Agard, D. A. (1989) Nature 341, 462-464; Baker, D., et al. (1992) Nature 356, 263-265]. The pro region also acts as a potent inhibitor of the mature enzyme [Baker, D., et al. (1992) Proteins: Struct.,Funct., Genet. 12, 339-344]. This inhibition is mediated through direct steric occlusion of the active site by the C-terminal residues of the pro region [Sohl, J. L., et al. (1997) Biochemistry 36, 3894-3904]. Through mutagenesis and structure-function analyses we have begun to investigate the mechanism by which the pro region acts as a single turnover catalyst to facilitate folding of the mature protease. Of central interest has been mapping the interface between the pro region and the protease and identifying interactions critical for stabilizing the rate-limiting folding transition state. Progressive C-terminal deletions of the pro region were found to have drastic effects on the rate at which the pro region folds the protease but surprisingly little effect on inhibition of protease activity. The observed kinetic data strongly support a model in which the detailed interactions between the pro region C-terminus and the protease are remarkably similar to those of known substrate/inhibitor complexes. Further, mutation of two protease residues near the active site have significant effects on stabilization of the folding transition state (kcat) or in binding to the folding intermediate (KM). Our results suggest a model for the alpha-lytic protease pro region-mediated folding reaction that may be generally applicable to other pro region-dependent folding reactions.

Amino Acid Sequence↗
PubMed1998

GDNF is abundant in the adult rat gut.

Glial derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system (ENS). Although previous work has measured GDNF mRNA levels, little is known about the concentration of GDNF protein produced in developing or adult tissues. The aim of this study was to quantitate the concentration of GDNF protein in various tissues of the developing and adult rat and in adult human gut. A two site antibody immunoassay was used to quantitate GDNF using recombinant rat GDNF as a standard. In the adult rat gastrointestinal tract the intestine contained the highest concentration of GDNF while the stomach and esophagus have the lowest concentrations. The isolated muscular wall of the intestine has approximately four times the GDNF concentration of the intact intestine. Other tissues with smooth muscle such as the aorta and urinary bladder contain moderate GDNF concentrations. In contrast, GDNF is barely detectable in the adult kidney and liver. High concentrations of GDNF were also detected in human colon and jejunum. As development proceeds in the rat, there is a tendency for the concentration of GDNF to increase in the intestine but decrease in other tissues. Treatment of the jejunum with the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC) results in an increase in the number of smooth muscle cells, a decrease in myenteric neurons, and an increase in the concentration of GDNF in homogenates of intestine. The observations that GDNF concentrations are high in the adult intestine suggest that this growth factor may be important for the maintenance of the adult ENS.

Adult↗
PubMed1998

Evaluation of catheter-mounted transducers for intra-oesophageal pressure recording in respiratory function tests.

Oesophageal pressure measurements in respiratory function tests are commonly performed using a balloon-catheter system. This study investigates the usefulness of catheter-mounted pressure transducers as an alternative to balloon-catheter systems. Calibration related physical properties of the catheter mounted pressure transducers are evaluated in vitro. The behaviour of these transducers in vivo is evaluated in ten volunteers by relating pressures measured in the oesophagus to airway opening pressures and by comparing these relationships with those sequentially obtained by a balloon-catheter system. The catheter-mounted pressure transducers show no drift after a proper preparation procedure. These catheters, with integrated pressure transducers, are tolerated significantly better by the subjects than are balloon catheters. The catheter-mounted pressure transducers are found to give an equivalent performance compared with the balloon-catheter system, if relative pressures are of interest. However, unpredictable and uncontrollable shifts in offset occur during the in vivo measurements, disturbing absolute pressure readings. Possible explanations for these shifts are the presence of bubbles and adhesion of mucus to the transducers, exerting Van der Waals forces, and contact with the tissue of the oesophageal wall. These shifts are found to be quite stable throughout a period of measurement and therefore of minor disturbance to relative pressure measurements, for instance in assessing the elastic properties of lungs.

Adult↗
PubMed1998

Procoagulant and proinflammatory activity in acute coronary syndromes.

OBJECTIVES: Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes. METHODS: Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA). RESULTS: FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups. CONCLUSIONS: IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Angina, Unstable↗
PubMed1998

An analogue laser optical disc in comparison with cinefilm for visual analysis of coronary narrowings before and after coronary angioplasty.

This study evaluated an analogue laser optical disc (MVP) as an alternative for cinefilm angiography in the visual analysis of coronary angiograms. Visual analysis was performed independently by 5 observers using cinefilm and MVP before and after PTCA (194 coronary lesions in 88 patients) and the outcomes were compared with QCA. The mean percentage diameter stenosis on cinefilm and MVP yielded similar results compared to QCA. Regression analysis showed a good correlation between the mean cinefilm and MVP values per diameter stenosis (p < 0.001). Bland-Altman plots confirmed these findings. Qualitative analysis for detection of coronary dissections after PTCA showed an incidence of 31.3% (cinefilm) and 21.8% (MVP) (p < 0.05). The results of this study indicate that the visual analysis of the coronary angiograms using the analogue laser optical disc (MVP) yields similar results compared to the cinefilm concerning coronary lesion severity, although there is an underestimation of coronary dissections.

Adult↗
PubMed1998

Suppression of torsades de pointes by atropine.

A 67 year old woman with a history of chronic atrial fibrillation presented with asthma cardiale. She took no medication and there was no family history of long QT syndrome. She was treated with furosemide, nitroprusside, acenocoumarol, and digoxin. Two days later excessively prolonged RR intervals, which were terminated by escape beats with a right bundle branch block morphology, suggested impending total AV block. There was also severe QT (0.48 s) and QTc (0.56) interval prolongation with bizarre inverted TU waves and multifocal premature ventricular complexes within the U waves. The patient experienced angina pectoris followed by episodes of torsades de pointes, which were interpreted as the result of bradycardia, and the bradycardia as the result of high grade AV block induced by increased vagal tone caused by ischaemia in the presence of digoxin intoxication (serum digoxin was 2.5 micrograms/l). Subsequent atropine infusion sped up the ventricular rate and shortened the QT (0.39) and QTc (0.51) intervals. Digoxin was replaced by metoprolol to control ventricular rate and angina pectoris. Within days, QT and QTc intervals became normal and the U waves disappeared. Neither torsades de pointes nor angina pectoris recurred. Based on a review of the literature, it is suggested that the electrophysiological mechanism of this effect is not only an increase of the heart rate, but also a direct action of muscarinic receptor antagonism on Purkinje cells and ventricular refractoriness.

Aged↗
PubMed1998

Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study. Fraxiparin Anticoagulant Therapy in Myocardial Infarction Study Amsterdam (FATIMA) Study Group.

OBJECTIVE: To investigate the feasibility of fixed dose, weight adjusted subcutaneous low molecular weight heparin (LMWH), with monitoring of anti-Xa levels and assessment of coronary patency rates after three to five days, thereby giving an initial indication of its safety and efficacy. DESIGN: In 30 patients with acute myocardial infarction, LMWH (nadroparine) was given as a body weight adjusted intravenous bolus with thrombolysis (rt-PA infusion) and in weight adjusted subcutaneous doses at six hours, and every 12 hours thereafter for 72 hours. The target range was defined prospectively as 0.35-0.70 anti-factor Xa activity (aXa) units. The aXa level was measured every six hours. Coronary angiography was performed in all patients within five days after the start of thrombolytic treatment to determine patency (TIMI 2 and 3 flow) of the infarct related artery. RESULTS: The mean (SEM) aXa level over 72 hours was 0.52 (0.08) U/ml; from 12 hours onwards 88% of all aXa measurements were within the target range. At angiography, a patent infarct related artery was present in 24 of the 30 patients. No major bleeding complications occurred, though minor bleeding complications were observed in two patients. CONCLUSIONS: This small study indicates that LMWH is feasible as an adjunct to thrombolysis in patients with acute myocardial infarction. The aXa levels were within the target range and patency rates at three to five days were around 80%, with no major bleeding complications.

Adult↗
PubMed1998

Heat generation during ultrasonic instrumentation of dentin as affected by different irrigation methods.

Heat is produced by magnetostrictive ultrasonic scalers which may cause injury to pulpal and periodontal tissues. Water coolant flows around the instrument stack and is directed at the instrument tip to reduce the generation of heat. Sound surgical practice requires the use of a sterile coolant for ultrasonic scaling during surgery. Intermittent bulb irrigation is one way to deliver sterile coolant when using ultrasonic scalers not equipped with a dedicated sterile water reservoir. The purpose of this study was to compare the temperature rise in dentin during ultrasonic scaling using either ultrasonic handpiece irrigation or intermittent bulb irrigation. Twenty dentin/cementum root slabs were prepared for each thickness of 0.5, 1.5, and 2.5 mm. A 3.0 mm x 1.5 mm field was outlined on each slab to indicate the area of intended instrumentation. Each slab was mounted such that a thermocouple placed in contact with dentin opposite the area of instrumentation was shielded from irrigation. Twenty samples of each thickness were ultrasonically scaled during which dentin temperature was recorded every 5 seconds over a 30-second period. All 60 slabs were first treated with dental unit ultrasonic handpiece water irrigation, followed by no irrigation, and finally by bulb irrigation with sterile saline. Repeated measures analysis of variance indicated that there were differences among the three treatment groups for temperature change over the course of the study (P < 0.001). Dentin temperature increased with both decreasing slab thickness and with increasing duration of instrumentation. However, only scaling without irrigation produced a rise in dentin temperature from baseline to a level reported as deleterious to pulpal and periodontal tissues. Bulb syringe irrigation delivered as a continuous drip and ultrasonic unit water spray minimized heat generation to physiologically tolerable levels. Intermittent bulb irrigation appears to be a satisfactory alternative to use of ultrasonic scaler water spray for cooling during ultrasonic scaling at surgery.

Analysis of Variance↗