Search PubMed⌕ Search

Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

At least 289 records · Page 16Linked to original sources
PubMed1991

The effect of inhaled corticosteroids on the maximal degree of airway narrowing to methacholine in asthmatic subjects.

Airway hyperresponsiveness in asthma is characterized by an increase in sensitivity and in maximal response to airway-narrowing stimuli. Long-term therapy with inhaled corticosteroids is known to reduce airway hypersensitivity in asthmatic patients. To investigate whether these drugs also reduce the maximal degree of airway narrowing we studied the effects of inhaled budesonide on the maximal response plateau of the dose-response curve to inhaled methacholine in mildly asthmatic patients in whom a raised plateau could be measured. Sixteen atopic patients with mild asthma were placed randomly into two parallel treatment groups to receive double-blindly either budesonide (400 micrograms twice daily) or placebo, inhaled via a Turbuhaler, for 4 wk. Before treatment, after 2 and 4 wk of treatment, and after 2 and 4 wk of wash-out, complete dose-response curves to methacholine were obtained using a standardized 2-min tidal breathing method. The response was measured by FEV1, expressed in % fall from baseline. A plateau on the log dose-response curve was considered if three or more data points fell within a 5% response range. The maximal response was obtained by averaging the values on the plateau (MFEV1), and the sensitivity was calculated from the provocative concentration of methacholine, causing a 20% fall in FEV1 (PC20). After 4 wk of budesonide treatment, mean MFEV1 decreased from 41.6 to 33.7% fall (p = 0.0004). The changes in MFEV1 were significantly different between placebo and budesonide (p = 0.03). The geometric mean PC20 increased from 3.4 to 6.3 mg/ml (p = 0.02), but the changes in PC20 were not different between the two groups (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Bhattacharya: a new application for quality control.

The Bhattacharya method and the 'average of normals' method for internal quality control were compared. Both are based on unselected patient test results. The Bhattacharya method is mostly used in clinical chemistry for calculation of reference intervals but could be modified for quality control procedures. Using the data of a coagulation test and stimulating systematic errors, it was concluded that the Bhattacharya method is more sensitive to expected shifts and is more flexible than the 'average of normals' method.

Blood Coagulation Tests↗
PubMed1991

The neural crest as a possible pathogenetic factor in coarctation of the aorta and bicuspid aortic valve.

Patients (n = 109) operated on for coarctation of the aorta were analyzed for occurrence of associated cardiac and noncardiac anomalies. Attention was also paid to the prevalence of cardiac anomalies in the relatives of these patients. Of the patients with coarctation of the aorta, 57 (52%) had a bicuspid aortic valve. Forty-three (39%) of the 109 patients had one or more noncardiac anomalies. In 29 (27%) patients the noncardiac anomaly involved the head/neck structures. Noncardiac anomalies were much more prevalent in patients with coarctation and bicuspid aortic valve, especially anomalies involving the head/neck structures: 44% compared to 8% of patients with a normal aortic valve. Congenital cardiac malformations were present in relatives in the first or second degree of 18% of the patients. Bicuspid aortic valve was more prevalent in patients with an affected relative (75%) than in patients with unaffected relatives (47%). Recent studies showed that the neural crest plays an important role in the development of cardiac and a variety of noncardiac structures. The cardiac structures derived from the neural crest involve the outflow tract of the heart and the aortic arch system. Maldevelopment of neural crest cells could therefore be responsible for the combined occurrence of outflow tract (e.g., bicuspid aortic valve), aortic arch (e.g., coarctation), and noncardiac anomalies. This study supports the concept that some anomalies of the aortic arch system, including aortic coarctation, are cardiovascular manifestations of a spectrum of anomalies involving the head and neck region that may be due to a genetic-environmental disorder of the neural crest.

Aortic Coarctation↗
PubMed1991

Radionuclide angiography with technetium-99m in vivo labeled erythrocytes does not lead to induction of mutations in the HPRT gene of human T-lymphocytes.

Mutant frequencies were measured in T-lymphocytes of patients undergoing radionuclide angiography with erythrocytes labeled in vivo with technetium-99m. Blood from 13 patients was sampled before and after (8-120 days) an injection with 750 MBq technetium-99m. Frequencies of HPRT- mutants were measured with the T-cell cloning method. Results indicated that the mean frequency of mutants after treatment was significantly below that measured before exposure. Thus, in contrast to published data, our results do not support the conclusion that radionuclide angiography with technetium-99m induces HPRT- mutations. Further analysis of our data indicated that the decrease in mutant frequency after exposure can be accounted for by an effect of cloning efficiency.

Adult↗
PubMed1991

Discordance of visual and quantitative analysis regarding false negative and false positive test results in thallium-201 myocardial perfusion scintigraphy.

Visual assessment and quantitative analysis of exercise thallium-201 myocardial perfusion scintigraphy was performed in 203 consecutive patients who underwent coronary arteriographic studies to identify the factors associated with false negative and false positive studies. Also the discordance between visual and quantitative analysis was evaluated. One hundred sixty-two (80%) of these 203 patients had significant coronary artery disease (CAD), i.e. a luminal stenosis greater than or equal to 50%. Fifty-two (32%) of these 162 patients with documented CAD showed negative thallium results either by visual or quantitative analysis. When interpreted visually 36/162 (22%) of patients were judged as negative, and when analyzed quantitatively 41/162 (25%) of patients were judged as negative (ns). Of the total group of 52 patients with false negative visual and/or quantitative analysis test results, 27 (17%) showed discordance between these two methods. Of the 41 patients without significant CAD, 12 (29%) showed positive thallium findings. Visual interpretation was positive in 9/41 (22%) of patients without significant CAD, and quantitative analysis in 5/41 (12%) (ns). Of the total group of 12 patients with positive visual and/or quantitative analysis test results, 10 (24%) showed discordance between these two methods. Therefore, in the total group, 37 patients (18%) showed discordance between visual and quantitative analysis. It is concluded that 1) the sensitivity and the specificity of visual interpretation and quantitative analysis of thallium-201 exercise scintigraphy for detecting CAD is similar, and 2) that there is frequent discordance of visual interpretation and quantitative analysis in thallium-201 exercise scintigraphy.

Coronary Disease↗
PubMed1990

The measurement of change of quality of life in clinical trials.

A model is presented for the measurement of change of quality of life in clinical trials with time under the influence of one or more treatments. Quality of life is regarded as a multidimensional latent variable, and is measured through dichotomous item responses on a number of points in time. Change of quality of life is 'explained' with a latent logistic regression model which may include parameters for the time process, the effects of clinical treatments, and interaction parameters. By assuming the absence of patient/time interaction within treatment groups, the parameters of the time process and the treatment effects can be estimated independently of the latent quality of life parameters at the start of the treatment. Consequently, differential mortality, censoring mechanisms, and other mechanisms causing missing data can be ignored.

Breast Neoplasms↗
PubMed1990

Is quantitative analysis superior to visual analysis of planar thallium 201 myocardial exercise scintigraphy in the evaluation of coronary artery disease? Analysis of a prospective clinical study.

Quantitative analysis of myocardial exercise scintigraphy has been previously reported to be superior to visual image interpretation for detection of the presence and extent of coronary artery disease. Computer analysis of perfusion defects and washout rate of thallium 201 was performed on scintigrams from a group of 131 consecutive patients (prospective group), using criteria defined from a previous group of 72 patients (initial group), and compared with visual interpretation of scintigrams for detection and evaluation of coronary artery disease. The sensitivity of the quantitative technique with regard to overall detection of coronary artery disease was not significantly different from the visual method (69% and 74%, respectively), whereas the specificity was higher (86% and 68%). Quantitative analysis did not increase the sensitivity of thallium imaging over the visual method in the left anterior descending artery (46% vs 65%) and the right coronary artery (51% vs 72%) but did increase sensitivity in the left circumflex artery (75% vs 47%). Whereas in the initial group quantitative analysis resulted in a better identification of multivessel disease (sensitivity 81% vs 57%), in the prospective group sensitivity decreased (54% vs 67%) without significant loss of specificity. The initial group had a 40% incidence of three-vessel disease and the prospective group, 22% (P less than 0.05). One-vessel disease was higher in the prospective group (32% vs 11%, P less than 0.05). Thus, assessing the quantitative technique in a larger prospective patient population, there was no improvement of detection of the presence and extent of coronary artery disease when compared with visual interpretation.

Coronary Disease↗
PubMed1990

Improvement of diagnosis in the non-invasive assessment of coronary artery disease: enhanced evaluation of quantitative exercise 201thallium imaging by multivariate analysis.

STUDY OBJECTIVE: The aim was to evaluate discriminant analysis, performed in patients without prior myocardial infarction, in enhancing the diagnostic value of quantitative exercise 201thallium scintigraphy. DESIGN: All clinical, electrocardiographic, and scintigraphic variables were first subjected to a univariate analysis. Afterwards a discriminant analysis was done. PATIENTS: 135 patients (104 male) were studied. Age was 24-70 years, mean 55 years. MEASUREMENTS AND MAIN RESULTS: Two discriminant analyses were done. In the first analysis, the ability to detect the presence of coronary artery disease was tested. Significant variables were: (1) history of angina, (2) sex, (3) quantitative analysis of 201thallium scintigraphy, (4) age, (5) ischaemic ST response, (6) angina during the test, and (7) the pressure-rate product. The sensitivity, specificity, and accuracy of classification using the discriminant function were 91%, 87%, and 90%, respectively. The sensitivity was higher than when using only visual interpretation (sensitivity 70%; p less than 0.0002) or quantitative interpretation (sensitivity = 66%; p less than 0.0001) of thallium scans, without significant loss of specificity (p less than 0.5488; p less than 0.6875). In the second analysis, a discriminant function was calculated to detect multivessel disease. Five input variables were selected: (1) number of vessels with stenosis predicted by quantitative analysis, (2) number of vessels with stenosis predicted by visual analysis, (3) ischaemic ST response, (4) sex, (5) angina during the test. Multivariate analysis showed an increase in sensitivity when compared with visual interpretation (78% v 55%; p less than 0.0043) and quantitative analysis (66%; p less than 0.0156). Using the classification, the discriminant function was more accurate than visual analysis (81% v 69%) or quantitative analysis (77%). CONCLUSIONS: The results show that multivariate analysis of non-invasive test results in quantitative thallium exercise testing allows convenient use for clinical purposes with improved results.

Adult↗
PubMed1990

Comparative value of visual and quantitative analysis of thallium-201 imaging after exercise in patients with an abnormal baseline repolarization on the electrocardiogram at rest.

In this study the role of visual assessment and quantitative analysis of thallium-201 myocardial stress perfusion scintigraphy (MPS) was evaluated in patients with a normal electrocardiogram (ECG) (group I) and in patients with an abnormal baseline repolarization on the ECG (group II). One-hundred-and-thirty-five patients were studied. Group I consisted of 93 patients, 65 of whom had coronary artery disease (CAD), i.e. a luminal stenosis of greater than or equal to 50%; group II consisted of 42 patients, 32 of whom had CAD. In group II the exercise ECG was considered uninterpretable and thus only visual and quantitative analysis of MPS was investigated. Sensitivity and specificity of exercise electrocardiography, visual assessment and quantitative analysis of MPS were not significantly different in group I: sensitivities of the three methods were 66, 62 and 55% respectively, and specificities 86, 79 and 96% respectively. In group II there were no significant differences in the sensitivities and specificities of visual assessment or quantitative analysis of MPS: sensitivities of the two methods being both 88% and specificities both 80%. Visual assessment of redistribution (P less than 0.05) and quantitative analysis of washout (P less than 0.005) was significantly superior in group II than in group I; probably because of a higher incidence of three-vessel disease in the second group.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1990

Effector mechanisms in graft-versus-host disease in response to minor histocompatibility antigens. I. Absence of correlation with cytotoxic effector cells.

Cell-mediated immunity against minor histocompatibility (mH) antigens is assumed to contribute to the development of graft-vs.-host disease in recipients of HLA-identical bone marrow grafts. To investigate the role of antihost-specific cytotoxic effector cells, we analyzed patients' T cell cultures after transplantation, in a chromium release assay using T lymphoblasts from patients and donors as target cells. Sixteen patients were studied between 1 and 25 months after grafting. Specific antihost cytotoxic T cell activity was detected in 4 of 5 patients with acute GVHD and in 5 of 5 patients with chronic GVHD, but also in 5 of 6 patients without any clinical signs of GVHD. Generally, the antihost Tc cell activity appeared within the first 3 months, increased to a maximum between 3 and 6 months, and gradually disappeared thereafter. This time effect was significant (P = 0.002). There was a suggestive trend in patients with chronic GVHD toward developing higher and more persistent levels of antihost Tc cell activity than in those without GVHD. Yet, these results can no longer support our earlier finding that the generation of antihost Tc cells is associated with the development of GVHD, since antihost Tc cells could be generally detected whether or not GVHD occurred. Our findings do not a priori exclude an effector cell role for Tc cells in GVHD but strongly indicate that other risk factors must be involved as well.

Adolescent↗
PubMed1990

Effector mechanisms in graft-versus-host disease in response to minor histocompatibility antigens. II. Evidence of a possible involvement of proliferative T cells.

To study helper T cell activation against minor histocompatibility (mH) antigens of the host after HLA-identical bone marrow transplantation, patients' lymphocytes collected longitudinally after transplantation were tested in a primed lymphocyte test using PBL from patients and donors as stimulator cells. Sixteen patients were studied between 1 and 25 months after grafting. Antihost Th cells were detected in 10 patients. Optimum levels of antihost activity were generally reached within the first 3 months, thereafter two patterns were identified; in some patients the antihost Th cell activity persisted for at least 2 years, whereas in other patients a decline was observed with time. Antihost Th cell activity developed in each of 5 patients with acute GVHD, in 3 out of 5 patients with chronic GVHD, but in only 2 out of 6 patients without GVHD. The average antihost Th cell activity in patients with acute GVHD was significantly higher than in patients without GVHD (P = 0.036) and was also higher, although not significantly, than in patients with chronic GVHD. These findings indicate that, in man, as was shown in studies in mice, helper T cells do participate in the response to mH antigens. Although other mechanisms may also be involved, we here propose that mH antigen-specific Th cells may be a risk factor for acute GVHD.

Adolescent↗
PubMed1990

Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background.

The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements.

Absorptiometry, Photon↗
PubMed1989

Detection of multivessel disease in patients with sustained myocardial infarction by thallium 201 myocardial scintigraphy: no additional value of quantitative analysis.

This study was performed to determine the value of visual and quantitative thallium 201 scintigraphy for the detection of multivessel disease in 67 patients with a sustained transmural myocardial infarction. Also the viability of the myocardial regions corresponding to pathologic Q-waves was evaluated. Of the 67 patients, 51 patients had multivessel coronary artery disease (76%). The sensitivity of the exercise test was 53%, of thallium scintigraphy 69%, when interpreted visually, and 67%, when analysed quantitatively. The specificity of these methods was 69%, 56%, and 50%, respectively. Sixty-two infarct-related flow regions were detected by visual analysis of the thallium scans, total redistribution was observed in 11/62 (18%) of patients, partial redistribution in 26/62 (42%), and no redistribution in 25/62 (40%) of patients. The infarct-related areas with total redistribution on the thallium scintigrams were more likely to be associated with normal or hypokinetic wall motion (7/11: 64%) than the areas with a persistent defect (7/25:28%) (P = 0.05), which were more related with akinetic or dyskinetic wall motion. Based on our results, it is concluded that 1) both visual and quantitative analysis of thallium exercise scintigraphy have limited value to predict the presence or absence of multivessel coronary artery disease in patients with sustained myocardial infarction, and 2) exercise-induced thallium redistribution may occur within the infarct zone, suggesting the presence of viable but jeopardized myocardium in presumed fibrotic myocardial areas.

Coronary Angiography↗
PubMedDate not supplied

Measurement of frequencies of HPRT mutants, chromosomal aberrations, micronuclei, sister-chromatid exchanges and cells with high frequencies of SCEs in styrene/dichloromethane-exposed workers.

Frequencies of HPRT mutants (MFs), chromosomal aberrations with or without gaps (CA+; CA-), aberrant cells (AC), micronuclei (MN), sister-chromatid exchanges (SCEs) and cells with high frequencies of SCEs (HFCs) were measured in lymphocytes collected from 46 workers occupationally exposed to styrene and dichloromethane (DCM = methylene chloride). These parameters were also determined in 23 controls. Time-weighted average (TWA) values for styrene and DCM exposure during an 8-h working day were respectively 70 mg/m3 (range: 0-598) and 108 mg/m3 (range: 0-742). These values correspond to TWA values of 17 ppm styrene and 31 ppm DCM. In exposed workers, all cytogenetic parameters were significantly enhanced (P < 0.0001; one-sided), but, due to the lack of appropriate control data, no definite conclusions could be drawn concerning the mutagenicity of styrene/DCM exposure. Duration of exposure was not correlated with genetic effects analyzed. The TWA value for styrene was not correlated with the extent of genetic damage detected, but the TWA value for DCM was positively correlated with the frequencies of chromosome aberrations (with gaps) and aberrant cells. These observations make it difficult to decide whether styrene or DCM, or both chemicals, induced the cytogenetic effects observed in exposed workers. Using the present styrene/DCM data, earlier ethylene oxide data and unpublished epichlorohydrin data, the relative sensitivity of the genetic endpoints to detect genotoxic exposure was: HFC > CA- > CA+ > SCE > MN > HPRT.

Adult↗
PubMedDate not supplied

Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries.

Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatheterized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate-pressure product than group II patients; all had normal findings by physical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had signs of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria for abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality.

Adult↗
PubMedDate not supplied

Detection of coronary artery disease: comparison between technetium 99m-labeled sestamibi single-photon emission computed tomography and two-dimensional echocardiography with dipyridamole low-level exercise-stress.

BACKGROUND: Myocardial perfusion imaging in conjunction with dipyridamole low-level exercise stress has proved its value in the evaluation of patients with coronary artery disease (CAD). Simultaneous wall motion analysis by two-dimensional (2D) echocardiography may provide additional information beyond that obtained by myocardial perfusion imaging alone. The purpose of this study was to compare 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) and 2D echocardiography for the evaluation of CAD according to a dipyridamole low-level bicycle exercise stress protocol. METHODS AND RESULTS: We studied 35 consecutive patients referred for the evaluation of chest pain who had undergone coronary arteriography. 99mTc-labeled sestamibi SPECT and 2D echocardiography agreed in 27 patients (80%) studied for overall detection of CAD. On a segmental basis, agreement was found between SPECT and 2D echocardiography in 124 (73%) of 170 segments (Cohen's kappa = 0.43). The accuracy of the combined assessment of myocardial perfusion and echocardiographic wall motion in detecting CAD was 86%, which was not different from the accuracy of SPECT alone (80%; difference not significant) but significantly higher than for 2D echocardiography alone (71%; p = 0.03). In the detection of individual coronary artery stenoses, SPECT had a significantly higher accuracy for detecting left anterior descending coronary artery lesions than had 2D echocardiography (80% vs 60%; p < 0.01); combining the two method did not improve the accuracy (80%). The combined assessment slightly improved the accuracy for detecting left circumflex coronary artery stenoses from 71% to 83% (p = 0.05). CONCLUSION: The combined simultaneous assessment of myocardial perfusion by 99mTc-labeled sestamibi SPECT and wall motion by 2D echocardiography did not significantly improve overall accuracy over that obtained by 99mTc-labeled sestamibi SPECT alone. Therefore 99mTc-labeled sestamibi SPECT with dipyridamole low-level exercise stress appears the preferred imaging modality for the evaluation of patients with CAD.

Adult↗