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Biomedical subjects

J L Willems

Publications and source records attributed to J L Willems.

At least 19 recordsLinked to original sources

[Distinction between renal and nonrenal hematuria using immunoperoxidase staining of erythrocytes in urine for Tamm-Horsfall protein].

A recently described immunocytochemical staining method to distinguish renal from non-renal haematuria was adapted for use in the standard clinical chemical laboratory. The method is based on the observation that only in case of renal haematuria are erythrocytes in urine coated with so-called Tamm-Horsfall protein, originating from the renal tubuli. Erythrocytes in urine were stained using an indirect immunoperoxidase method, resulting in cells with dark-brown stained surfaces. The staining methods were validated with material from clinically diagnosed cases of haematuria of renal or non-renal origin and compared with scores of the number of dysmorphic erythrocytes, another method to distinguish renal from non-renal haematuria. In specimens of presumed strictly renal haematuria 86% (SD 8.7; n = 26) of the erythrocytes stained immunocytochemically. However, in specimens of haematuria originating from bleeding in the renal pelvis few cells stained (6%; SD 5.8; n = 4). In specimens of purely non-renal haematuria only 13% (SD 13.5; n = 21) stained. Immunocytochemical staining of erythrocytes permitted a much better distinction between renal and non-renal haematuria, with better sensitivity and specificity, than the inspection of erythrocyte morphology. We conclude that immunochemical staining of erythrocytes in urine is a valuable method for distinguishing renal and non-renal haematuria.

Diagnosis, Differential

Improvement of automated electrocardiographic diagnosis by combination of computer interpretations of the electrocardiogram and vectorcardiogram.

In the international project "Common Standards for Quantitative Electrocardiography" (CSE), diagnostic results of different computer programs for the interpretation of the electrocardiogram (ECG) and of the vectorcardiogram (VCG) were combined, and it was shown that the "combined program" performs better than each program separately. Because the program MEANS (Modular ECG Analysis System) comprises 2 different classification programs--one for the ECG, the other for the VCG--this allowed investigation of whether the combined interpretations would yield a better diagnostic result than either one separately. This approach requires that a VCG always be recorded in addition to the ECG. To circumvent this complication, the VCG was reconstructed from the simultaneously recorded ECG leads. This reconstructed VCG was then interpreted by the VCG classification program, whereupon the diagnostic interpretations of the ECG and the reconstructed VCG were combined. For the validation, the CSE database of documented ECGs and VCGs (n = 1,220) was used. The combination of the ECG and VCG interpretations yielded a better diagnostic result than each interpretation program separately (total accuracy 74.2% (ECG + VCG) vs 69.8% (ECG) and 70.2% (VCG), p less than 0.001 in both cases). The results for the reconstructed VCG (total accuracy 70.5%) are comparable to those for the ECG and the VCG (p greater than 0.10 in both cases). The performance of the combined interpretations of ECG and reconstructed VCG (total accuracy 73.6%) is approximately the same as that of the combined ECG and VCG (p greater than 0.10). Thus, the performance of an ECG computer program can be improved by incorporating both ECG and VCG classificatory knowledge, using only the ECG itself.

Diagnosis, Computer-Assisted

Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris.

To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris.

Angina Pectoris

Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients.

Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg-1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1.

Dose-Response Relationship, Drug

The conservative coronary angioplasty strategy after thrombolysis for acute myocardial infarction: immediate and short-term results.

The in-hospital and short-term follow-up results of a conservative coronary angioplasty approach in 354 consecutive patients treated after thrombolysis for acute myocardial infarction were compared with results obtained in 408 control noninfarcted patients treated for the classical indication of myocardial ischemia. Only 20% of the study patients underwent angioplasty during the initial hospitalization period and the clinical success rate was 93% versus 95% in the control group (p = NS). No significant differences in the total number of in-hospital untoward events were observed (10.2% and 7.6%, respectively). During a 7.4 +/- 1.5 month follow-up period, the total number of adverse events was only 16.9% in the study patients but it was 27.8% in the control group (p < 0.001). There were no significant differences in death, myocardial infarction, or coronary surgery as individual events, but repeat angioplasty was less frequent in the study group (14.0% versus 21.5%, p < 0.01). Thus in-hospital results in patients undergoing angioplasty on a deferred basis after thrombolysis for myocardial infarction were largely comparable with those results obtained in noninfarcted patients. Moreover, short-term clinical follow-up events were reduced when compared with the control group, an observation apparently largely related to the subgroup without clinical evidence of residual ischemia.

Aged

Assessment of diagnostic ECG results using information and decision theory. Results from the CSE diagnostic study.

Information and decision theory were applied to assess the interpretation results of 15 computer programs (9 electrocardiogram and 6 vectorcardiogram) and 9 cardiologists; 8 of whom analyzed the electrocardiogram and 5 the vectorcardiogram, using a database of 1,220 clinically validated cases. The study demonstrates that information content and utility indices, by providing a comprehensive view of diagnostic performance, can enhance the insight given by the more classic statistical performance measures.

Cardiology

Quantitative assessment of 12-lead ECG synthesis using CAVIAR.

The objective of this study is to assess the performance of patient-specific segment-specific (PSSS) synthesis in QRST complexes using CAVIAR, a new method of the serial comparison for electrocardiograms and vectorcardiograms. A collection of 250 multi-lead recordings from the Common Standards for Quantitative Electrocardiography (CSE) diagnostic pilot study is employed. QRS and ST-T segments are independently synthesized using the PSSS algorithm so that the mean-squared error between the original and estimated waveforms is minimized. CAVIAR compares the recorded and synthesized QRS and ST-T segments and calculates the mean-quadratic deviation as a measure of error. The results of this study indicate that estimated QRS complexes are good representatives of their recorded counterparts, and the integrity of the spatial information is maintained by the PSSS synthesis process. Analysis of the ST-T segments suggests that the deviations between recorded and synthesized waveforms are considerably greater than those associated with the QRS complexes. The poorer performance of the ST-T segments is attributed to magnitude normalization of the spatial loops, low-voltage passages, and noise interference. Using the mean-quadratic deviation and CAVIAR as methods of performance assessment, this study indicates that the PSSS-synthesis algorithm accurately maintains the signal information within the 12-lead electrocardiogram.

Electrocardiography

Neurological aspects of organophosphate poisoning.

Besides their well-known anticholinesterase action resulting in a typical acute cholinergic crisis, organophosphorus (OP) agents are capable of producing several subacute or chronic neurological syndromes. The acute over-stimulation at the neuromuscular junction results in muscle fiber necrosis. The significance of this OP-induced myopathy in human intoxication is unknown. Organophosphate-induced delayed neuropathy (OPIDN) arises 1-3 weeks after exposure to some OP compounds all capable of remarkably inhibiting a distinct esterase called neuropathy target esterase (NTE) during a critical time period. An experimental hen model has been designed to screen new OP compounds as to their delayed neurotoxic effects. The recently described intermediate syndrome emerges 1-4 days after an apparently well-treated cholinergic crisis. It main clinical features are sudden respiratory paralysis, cranial motor nerve palsies, and proximal limb muscle and neck flexor weakness. Whether or not this is a separate entity in OP agent toxicology remains to be seen. Further studies are required to further determine its clinical and paraclinical characteristics and the actual type of underlying neuromuscular dysfunction involved.

Acetylcholine

A standard communications protocol for computerized electrocardiography.

In an international collaborative project aimed at producing common standards for quantitative electrocardiography, a standard communications protocol (SCP-ECG) was developed for computerized electrocardiography. The protocol consisted of standards for the interchange, encoding, and storage of digital ECG data. The work was performed in three distinct, but closely related, work-packages and in close collaboration with representatives from 13 manufacturers of computerized electrocardiographs from all over the world. The objectives and results of SCP-ECG are briefly described in this paper.

Computer Communication Networks

Are Wistar rats not susceptible to organophosphate-induced delayed neurotoxicity?

Male Wistar rats were sacrificed 12 weeks after single exposure to various organophosphate compounds. Peripheral nerves and skeletal muscles were examined light microscopically for the occurrence of a delayed polyneuropathy. Although unequivocal morphological hallmarks of OPIDN had been demonstrated in other rat strains using similar doses of TOCP or mipafox, we were unable to demonstrate any abnormality with these compounds. Normal findings were also obtained with fenthion, the delayed neuropathic potential of which is debated, and with paraoxon or parathion, which are both highly unlikely to cause OPIDN. These data indicate that the Wistar rat strain is highly likely to be resistant to OPIDN.

Animals

Localizing the site of hematuria by immunocytochemical staining of erythrocytes in urine.

We have further explored the immunocytochemical staining method to discriminate renal and nonrenal hematuria, reported by Abrass and Laird (Am J Kidney Dis 1987;9: 44-50). After fixation on slides with acetone, erythrocytes in urine were stained with antiserum against human Tamm-Horsfall protein. Reactions were made visible by using either a fluorescent second antibody or a biotinylated second antibody, avidin, and biotinylated horseradish peroxidase, producing an insoluble reaction product. The staining methods were validated with material from clinically diagnosed cases of hematuria of renal or nonrenal origin. In material from kidney transplantation patients, in samples from the catheter that were presumed to contain renal erythrocytes, 84.7% and 80.1% of the erythrocytes stained by the immunofluorescence and immunoperoxidase methods, respectively, whereas in samples from the catheter that were supposed to contain nonrenal erythrocytes, 9.3% and 13.1% of the cells stained. In a group of nontransplantation patients with various causes of renal hematuria, 87.3% and 89.8% of the erythrocytes in urine stained with the immunofluorescence and immunoperoxidase methods, respectively, whereas in samples from patients with hematuria of known nonrenal origin, 12.9% and 12.4% of the cells stained. Staining of erythrocytes in renal and nonrenal hematuria was significantly different (P less than 0.001) and better discriminated between renal and nonrenal hematuria than did inspection of the morphology of erythrocytes in urine.

Adolescent

The diagnostic performance of computer programs for the interpretation of electrocardiograms.

BACKGROUND: Computer programs for the interpretation of electrocardiograms (ECGs) are now widely used. However, a systematic assessment of various computer programs for the interpretation of ECGs has not been performed. METHODS: We undertook a large international study to compare the performance of nine electrocardiographic computer programs with that of eight cardiologists in interpreting ECGs in 1220 clinically validated cases of various cardiac disorders. ECGs from the following groups were included in the sample: control patients (n = 382); patients with left ventricular hypertrophy (n = 183), right ventricular hypertrophy (n = 55), or biventricular hypertrophy (n = 53); patients with anterior myocardial infarction (n = 170), inferior myocardial infarction (n = 273), or combined myocardial infarction (n = 73); and patients with combined infarction and hypertrophy (n = 31). The interpretations of the computer programs and the cardiologists were compared with the clinical diagnoses made independently of the ECGs, and the computer interpretations were compared with those of the cardiologists. RESULTS: The percentage of ECGs correctly classified by the computer programs (median, 91.3 percent) was lower than that of the cardiologists (median, 96.0 percent; P less than 0.01). The median sensitivity of the computer programs was also significantly lower than that of the cardiologists in diagnosing left ventricular hypertrophy (56.6 percent vs. 63.9 percent, P less than 0.02), right ventricular hypertrophy (31.8 percent vs. 46.6 percent, P less than 0.01), anterior myocardial infarction (77.1 percent vs. 84.9 percent, P less than 0.001), and inferior myocardial infarction (58.8 percent vs. 71.7 percent, P less than 0.0001). The median total accuracy level (the percentage of correct classifications) was 6.6 percent lower for the computer programs (69.7 percent) than for the cardiologists (76.3 percent; P less than 0.001). However, the performance of the best programs nearly matched that of the most accurate cardiologists. CONCLUSIONS: Our study shows that some but not all computer programs for the interpretation of ECGs perform almost as well as cardiologists in identifying seven major cardiac disorders.

Cardiology

Coronary hemodynamics and coronary flow reserve after intracoronary diltiazem in humans.

To analyze the effect of the calcium antagonist diltiazem on coronary hemodynamics, epicardial coronary artery diameter, coronary blood flow and coronary blood flow velocity were assessed at baseline and after a 0.5 mg intracoronary bolus of diltiazem in nonstenotic coronary arteries of awake humans. Patients (n = 20) were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 microgram/kg/min infusion; n = 10), and coronary flow reserve was measured before and after administration of diltiazem. There were significant increases in epicardial coronary artery diameter (10%; p = 0.0001) and coronary blood flow (30%; p = 0.0001) in all patients after administration of diltiazem. Whereas basal coronary blood flow velocity increased only slightly (7%; p = not significant), there was a significant decrease in coronary flow reserve (10%; p = 0.004). Increases in coronary diameter and blood flow after diltiazem were comparable in patients pretreated with placebo or nitrates. However, the decrease in coronary flow reserve was significant only in patients pretreated with placebo (19%; p = 0.0008). This reduction in coronary flow reserve could be due to "raising the floor" (increased baseline coronary blood flow) or "lowering the ceiling" (reduction of maximal coronary blood flow).

Adult

Immediate and short-term results of a 1988-1989 coronary angioplasty registry.

To determine the relevance of recent refinements in angioplasty technology to our particular practice, the records of 507 consecutive patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) at our center between October 1988 and May 1989 were reviewed. At the time of PTCA, 41% of these patients had class IV angina and 44% were identified as having multivessel disease. Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which 95 (13%) were chronic total occlusions. Overall, 69% of the 734 lesions were judged anatomically complex, and, in dilating these lesions, a rail-type device was used almost exclusively. Successful dilatation was achieved in 659 of the 734 (90%) attempted lesions. There were low incidences of the major complications of death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%). Acute rethrombosis occurred in 54 patients (11%). In these patients, initial strategy of repeat dilatation was successful in 38 of 47 patients (81%). Overall, primary clinical success at PTCA was achieved in 480 patients (95%). At a mean follow-up of 7.5 +/- 1.5 months in 497 of the study patients, the event-free rate (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary bypass surgery or recurrence of severe [class III to IV] angina) was 71%. In conclusion, despite the often complex coronary disease in patients currently presenting to our center, a high initial success rate and acceptable short-term outcome of PTCA was achieved.

Aged

Long-term prognosis of male patients with an isolated chronic occlusion of the left anterior descending coronary artery.

The purpose of this study was to determine the long-term prognosis of patients with an isolated total occlusion of the left anterior descending artery (LAD). A total of 173 male patients with a chronic LAD occlusion and less than 50% narrowing of the other coronary arteries (group I) was compared with a group of 177 male patients with only insignificant coronary artery disease and a normal left ventricular function (group II). Baseline characteristics of both groups were comparable except for the inclusion of 54 patients (31.2%) with moderately or markedly reduced left ventricular systolic function in group I. During an 8-year follow-up period there was a greater number of patients with cardiac events in group I when compared with group II: cardiac death 11.2% versus 0.6% (p less than 0.0001), myocardial infarction 12.7% versus 3.4% (p = 0.001), myocardial revascularization procedures 11.6% versus 3.4% (p = 0.04). Stepwise discriminant analysis showed that a reduced ejection fraction and a family history of coronary artery disease were the best predictors for these adverse cardiac events.

Belgium

Value of electrocardiographic scoring systems for the assessment of thrombolytic therapy in acute myocardial infarction. The European Cooperative Study Group for Recombinant Tissue Type Plasminogen Activator.

The value of the Selvester and Cardiac Infarction Injury Scores was assessed in a randomized, placebo-controlled study of intravenous recombinant tissue plasminogen activator (rt-PA) in 721 patients with acute myocardial infarction. Electrocardiograms (ECG) obtained at admission, 6 h and 10 to 22 days after the start of therapy were analysed. Patients with prior myocardial infarction or QRS duration greater than or equal to 120 ms were excluded, leaving 322 in the rt-PA group and 333 in the placebo group. Cumulative 72-h release of alpha-hydroxybutyrate dehydrogenase (HBDH) and global ejection fraction derived from angiography and nuclear scintigraphy were used as independent measures of infarct size. Predischarge results demonstrated a net benefit of rt-PA therapy, with the Selvester Score 11% lower (P less than 0.01) and the Cardiac Infarction Injury Score 5.4% lower (P = NS) in the rt-PA than the control group. Total enzyme release was reduced by 19.2% (P less than 0.001) in the rt-PA group. In patients with inferior infarction, neither enzyme release (r = 0.30 to 0.40) nor ejection fraction (r = 0.22 to 0.31) correlated well with the ECG indices of infarct size. In anterior infarction, the correlations were better, especially between the Selvester Score and enzyme release (r = 0.40 to 0.48) as well as ejection fraction (r = -0.48 to -0.67). It is concluded that ECG scoring systems, especially the Selvester Score, although imperfect are useful to assess thrombolytic therapy in clinical trials. However, their value for the management and assessment of thrombolytic therapy in individual patients is still limited.

Electrocardiography

Hemodynamic changes after subselective intracoronary administration of nisoldipine in humans.

Hemodynamic changes after the subselective intracoronary administration of 50 micrograms of nisoldipine were analyzed in 24 nonstenotic coronary arteries using a randomized, placebo-controlled, double-blind protocol. The following hemodynamic parameters were studied: (a) epicardial coronary artery diameter, assessed by quantitative angiography; (b) coronary blood flow velocity, measured by an intracoronary Doppler probe; (c) coronary blood flow, calculated from the above parameters; (d) coronary flow velocity reserve, assessed after intracoronary administration of 10 mg of papaverine hydrochloride; and (e) heart rate and arterial blood pressure. Since 3 patients were excluded due to unreliable Doppler signals, a total of 21 patients was eligible for complete analysis (placebo: n = 9; nisoldipine: n = 12). In placebo-treated patients, all studied parameters proved to be very stable on repeat measurement and no significant changes were found. In nisoldipine-treated patients, a significant increase in epicardial diameter (+19%; p = 0.0001) and coronary blood flow (+47%; p = 0.003) was found. The coronary blood flow velocity transiently increased after nisoldipine, with a maximum (+80%) after 2 min and returning to baseline within 10 min. Finally, nisoldipine resulted in a significant decrease in the coronary flow velocity reserve by 20% (p = 0.001). All coronary hemodynamic effects were observed in the absence of changes in heart rate and arterial blood pressure. Therefore, the present data demonstrate that nisoldipine acts as a potent dilator of epicardial as well as resistance vessels in nonstenotic human coronary arteries.

Blood Pressure

Changes in human coronary flow reserve after administration of intracoronary diltiazem.

Epicardial coronary artery diameter (ECAD), coronary blood flow velocity (CBFV), and coronary flow velocity reserve (CFVR) were analyzed at baseline and after a 500 micrograms i.c. bolus of diltiazem in nonstenotic coronary arteries of awake humans. Furthermore, patients (n = 25) were first randomized to pretreatment either with placebo (n = 12) or isosorbide dinitrate (0.5 micrograms/kg/min infusion) (n = 13). Diltiazem resulted in a significant increase in epicardial diameter (+10%; p = 0.001) and in coronary blood flow (CBF) (+30%; p = 0.0001). Whereas basal CBFV only slightly increased (+7%; NS), there was a significant fall in CFVR (-11%; p = 0.001). The increase in coronary diameter and CBF after administration of i.c. diltiazem was comparable in placebo- and nitrate-pretreated patients. The decrease in CFVR, however, was restricted to the placebo-pretreated patients (-21%; p = 0.0004). Apparently, diltiazem attenuated the CFVR but only in the absence of nitrates. Thus, diltiazem i.c. appears to enhance myocardial oxygen supply without deleterious effects on the distal coronary perfusion pressure.

Blood Flow Velocity