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Biomedical subjects

E J van Beek

Publications and source records attributed to E J van Beek.

At least 19 recordsLinked to original sources

Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-kappa B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential.

Animals↗

Design and initial evaluation of a low-cost 3-Tesla research system for combined optical and functional MR imaging with interventional capability.

A 3-Tesla research system has been developed for functional and interventional magnetic resonance imaging (MRI) procedures on animal models based on a low field niche spectrometer. Use of two stages of fourth harmonic frequency multiplication has allowed us to produce a high-frequency spectrometer with good frequency stability based on a low-frequency direct digital synthesizer. The system has been designed with the ability to introduce interventional tools such as biopsy needles, radiofrequency (RF) electrodes, and fiber optics for optical spectroscopy and thermal ablation as well as drug infusions to allow function to be studied in the presence of external challenges. Full MR-compatible physiologic support capability allows animals to be maintained in a stable condition over extended periods of study. Functional MR images have been acquired by using gradient echoes (TR/TE = 40/12 msec) from the rat whisker barrel cortex using electrical stimulation (5-V, 1.5-mA, 1-msec pulses at 5 Hz via two needle electrodes inserted into the rat whisker pad). Initial results using respiratory gas challenges of 100% N(2), 100% O(2), and 10% CO(2) have shown excellent agreement between single wavelength (633 nm) optical and functional MR time series with subsecond time resolution. The 1-mm copper electrodes for interventional radiofrequency ablation procedures were easily visualized in the superior colliculus by using gradient echo sequences. This novel, low-cost, high field system appears to be a useful research tool for functional and interventional studies of rat brain and allows concurrent optical spectroscopy. J. Magn. Reson. Imaging 2001;13:87-92.

Animals↗

Herniography: a prospective, randomized study between midline and left iliac fossa puncture techniques.

AIM: To determine whether an optimal site of injection exists for herniography. MATERIALS AND METHODS: This was a prospective, randomized study of 93 consecutive patients who were referred for herniography over a period of 9 months. Patients underwent either a left iliac fossa (LIF) or midline puncture. Parameters assessed included initial adequate needle placement, complications, pain scores and body mass index (BMI). The groups were compared using Chi-squared test for categorical data, Student's t-test for continuous data and the Mann-WhitneyU-test for skewed data, withP < 0.05 considered statistically significant RESULTS: Four complications were encountered (4%), and these were equally distributed between the two groups. Adequate initial positioning of the needle was similar in both groups. The volume of local anaesthetic used was correlated with discomfort using a pain scale: a volume of >6 ml resulted in significantly more pain. More frequent initial adequate needle placement was observed in thin patients (BMI < 45 kg/m(2)) with experienced operators. Conversely, increased body mass index resulted in more difficult needle placement. CONCLUSION: Herniography is a safe procedure with few complications. There was no significant difference comparing the midline and LIF approaches.Nadkarni, S.et al. (2001). Clinical Radiology56, 389-392.

Anesthetics, Local↗

Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism--a critical review.

AIM: To determine the validity of a normal pulmonary angiogram in the exclusion of pulmonary embolism (PE), based on the safety of withholding anticoagulant therapy in patients with a normal pulmonary angiogram. MATERIALS AND METHODS: A review of English reports published between 1965 and April 1999 was carried out. Eligible articles described prospective studies in patients with suspected PE and a normal pulmonary angiogram, who remained untreated and were followed-up for a minimum of 3 months. Articles were evaluated by two authors, using pre-defined criteria for strength of design. End points consisted of fatal and non-fatal recurrent thromboembolic events. A sensitivity analysis was performed, by removing one study at a time from the overall results and by comparing pre- and post-1990 publications. RESULTS: Among 1050 patients in eight articles included in the analysis, recurrent thromboembolic events were described in 18 patients (1.7% 95% CI: 1.0-2.7%). These were fatal in three patients (0.3% 95% CI: 0.02-0.7%). The recurrence rate of PE decreased from 2.9% (95% CI: 1.4-6.8%) before 1990 to 1.1% (95% CI: 0.5-2.2%) after 1990. CONCLUSION: It would appear that the ability to exclude PE by angiography has improved over the years, as indicated by recurrence rate of PE. The low recurrence rate of PE supports the validity of a normal pulmonary angiogram for the exclusion of PE.

Anticoagulants↗

Lung scintigraphy and helical computed tomography for the diagnosis of pulmonary embolism: a meta-analysis.

To assess the diagnostic value of lung scintigraphy and helical computed tomography (hCT) in patients with suspected pulmonary embolism (PE), all English-language articles that described lung scintigraphy and hCT in patients with suspected PE were retrieved. Articles were assessed for strength of methodology, based on nine a priori-defined criteria. Parameters of diagnostic accuracy and results of management studies were calculated and evaluated. Lung scintigraphy is diagnostic in approximately 50% of patients with suspected PE. A normal perfusion scan has a chance of recurrent PE in two of 693 patients (0.3%; 95% CI: 0.2-0.4%; fatal in 0.15%). A high-probability lung scan is correlated with angiographically proven PE in 308 of 350 patients (88%; 95% CI: 84-91%). Pulmonary embolism was proven in 385 of 1529 patients (25%; 95% CI: 24-28%) with a nondiagnostic lung scan. Helical CT studies were compared with angiography and lung scintigraphy in 1171 patients, with a prevalence of PE of 39%. The sensitivity and specificity of hCT was 283/320 (88%; 95% CI: 83-91%) and 374/408 (92%; 95% CI: 89-94%), respectively. Only one prospective management study using hCT was available. In patients in whom anticoagulants were withheld based on a normal hCT study, recurrent thromboembolic events occurred in six of 109 patients (5.5%; 95% CI: 2-12%), with one fatality (1%; 95% CI: 0.02-4.3%). Lung scintigraphy is evaluated extensively and yields a diagnostic result in 50% of patients. Helical CT has similar positive predictive value to a high-probability lung scan. However, the exact role of hCT in the management of patients with suspected PE needs to be determined in prospective studies.

Angiography↗

Pulmonary ventilation imaged by magnetic resonance: at the doorstep of clinical application.

Over the past few years, magnetic resonance imaging (MRI) has emerged as an important instrument for functional ventilation imaging. The aim of this review is to summarize established clinical methods and emerging techniques for research and clinical arenas. Before the advent of MRI, chest radiography and computed tomography (CT) dominated morphological lung imaging, while functional ventilation imaging was accomplished with scintigraphy. Initially, MRI was not used for morphological lung imaging often, due to technical and physical limitations. However, recent developments have considerably improved anatomical MRI, as well as advanced new techniques in functional ventilation imaging, such as inhaled contrast aerosols, oxygen, hyperpolarized noble gases (Helium-3, Xenon-129), and fluorinated gases (sulphur-hexafluoride). Straightforward images demonstrating homogeneity of ventilation and determining ventilated lung volumes can be obtained. Furthermore, new image-derived functional parameters are measurable, such as airspace size, regional oxygen partial pressure, and analysis of ventilation distribution and ventilation/perfusion ratios. There are several advantages to using MRI: lack of radiation, high spatial and temporal resolution and a broad range of functional information. The MRI technique applied in patients with chronic obstructive pulmonary disease, emphysema, cystic fibrosis, asthma, and bronchiolitis obliterans, may yield a higher sensitivity in the detection of ventilation defects than ventilation scintigraphy, CT or standard pulmonary function tests. The next step will be to define the threshold between physiological variation and pathological defects. Using complementary strategies, radiologists will have the tools to characterize the impairment of lung function and to improve specificity.

Animals↗

[Value of the 'non-diagnostic' lung scan--further classification as to the risk of pulmonary embolism not reliable].

OBJECTIVE: To determine to what extent the 'non-diagnostic' lung scans made because of a clinical suspicion of pulmonary embolism enable further determination of the risk of pulmonary embolism. DESIGN: Retrospective. METHOD: All non-diagnostic lung perfusion ventilation scans made in the Academic Medical Centre of Amsterdam in 1997 of 114 patients in succession (55 males and 59 females aged 27-85 years) were subjected to blind and independent re-evaluation by three observers (an experienced nuclear medicine expert, an experienced and an inexperienced intern) who, using a lung segment chart, estimated the risk of embolism as < 25%, 25-50%, 50-75% and > 75%. They did this first without and then with the chest X-ray. The findings were grouped on the basis of accordance or non-accordance with the pulmonary angiogram. The interobserver agreement was calculated by means of kappa statistics. RESULTS: Of 58 patients the lung scan could be compared with a chest X-ray and a pulmonary angiogram. In 43 patients with a normal angiogram the observers in an average of 50% of the scans estimated the risk of pulmonary embolism as < 25%, as against 25-50% in 27%, 50-75% in 9% and > 75% in 5%. In 15 patients with a deviant pulmonary angiogram, these figures were 22%, 38%, 20%, and 12%, respectively. The interobserver kappa for evaluation without chest X-ray was < or = 0.16, as against < or = 0.41% with the chest X-ray. CONCLUSIONS: A reliable classification of the risk of pulmonary embolism was not possible on the basis of non-diagnostic lung scans, regardless of whether the patient did or did not have pulmonary embolism. The interobserver variability was less when the lung scan was evaluated together with the chest X-ray, but even so it was unacceptably high.

Adult↗

Upper thoracic spinal fractures in trauma patients - a diagnostic pitfall.

The diagnosis of upper thoracic spinal fractures in multiple-trauma patients remains a challenge. The clinical findings are often difficult to detect, especially in the presence of other (extremity) fractures, head injuries or in patients on respiratory support. The findings of chest radiographs and plain spinal films are described in a series of 23 patients with an upper thoracic spinal fracture. Radiographs were retrospectively reviewed by an orthopaedic surgeon and a skeletal radiologist. Fractures were classified according to Magerl and type A1 and A2 compression fractures were excluded. The neurological outcome was assessed using the Frankel scale.Initially, the fracture was missed in 5 patients (22%), mainly due to concomitant life-threatening injuries. Fractures consisted of type A, B and C in one, 10 and 12 patients, respectively. The main findings were: loss of vertical height of vertebra with or without malalignment (21), widened paraspinal line (21), widened mediastinum (4) and no gross abnormalities (2). Neurological lesions were Frankel A, B, C and E in respectively 14, 1, 1 and 7 patients.Upper thoracic spinal fractures are easily missed in patients with multiple injuries. In patients with neurological symptoms CT and/or MRI is required as soon as the general condition of the patient permits this.

Adolescent↗

Strategies for the safe and effective exclusion and diagnosis of deep vein thrombosis by the sequential use of clinical score, D-dimer testing, and compression ultrasonography.

Patients with suspected deep vein thrombosis (DVT) are subjected to leg vein compression ultrasonography (CUS) that confirms DVT in only 20 to 30% of patients. A positive CUS is consistent with DVT irrespective of clinical score. The sequential use of a simple clinical score assessment, a rapid sensitive enzyme-linked immunosorbent assay (ELISA) D-dimer test and CUS to safely exclude DVT is promising. The clinical score is a validated clinical model of complaints, signs, and symptoms, on the basis of which a pretest clinical probability for DVT can be estimated as low, moderate, and high. The safe exclusion of DVT by a rapid sensitive D-dimer test in combination with clinical score or CUS necessitates a negative predictive value of more than 99%. The negative predictive value for DVT is determined by the sensitivity of the rapid ELISA D-dimer test and the prevalence of DVT in subgroups of outpatients with suspected DVT. The prevalence of DVT in outpatients with a low, moderate, and high clinical score varies widely from 3 to 10%, 15 to 30% and more than 70%, respectively. A negative rapid ELISA D-dimer and a low clinical score (prevalence DVT 3 to 5%) will have a very high negative predictive value of more than 99.5% to exclude DVT without the need of CUS testing. A negative ELISA D-dimer test and a first-negative CUS safely exclude DVT in patients with a moderate clinical score with a negative predictive value of more than 99.5%, therefore obviating the need to repeat CUS. The use of a rapid ELISA D-dimer testing in patients with a high clinical score is not recommended. A negative CUS, a low clinical score, and a positive ELISA D-dimer, even less than 1000 ng/mL exclude DVT with a nega tive predictive value of more than 99%. Patients with a negative CUS, but a positive ELISA D-dimer, and a moderate or high clinical score have a probability of DVT of 3 to 5% and 20 to 30%, respectively, and are thus candidates for repeated CUS testing. The proposed sequential use of the clinical score assessment, a rapid ELISA D-dimer test, and CUS will be the most cost-effective diagnostic strategy for DVT because of a significant reduction of CUS examinations and gain of time for the patient and physician in charge.

Algorithms↗

Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.

BACKGROUND: The main purpose of ventilation scanning, as adjunct to perfusion lung scintigraphy, in acute pulmonary embolism is to allow for the classification of segmental perfusion defects as mismatched, which is generally accepted as proof for the presence of pulmonary embolism. We examined whether this function of the ventilation scan could be replaced by the chest X-ray. METHODS: In 389 consecutive patients with suspected pulmonary embolism and at least one segmental perfusion defect we classified the ventilation/perfusion (V/Q) scan and chest X-ray/perfusion (X/Q) scan as either mismatched or matched. Furthermore we analyzed whether this comparison was different in subgroups of patients with concomitant congestive heart failure or chronic obstructive pulmonary disease. RESULTS: Overall agreement between the X/Q and V/Q scan diagnostic category was found in 341 of 389 patients (88%; 95% CI 84-92%). The positive predictive value for obtaining a mismatched V/Q scan result in case of a mismatched X/Q scan result was 86% (95% CI 81-90%). If the X/Q scan yielded only matched defects the V/Q scan resulted in the same classification in 90% (95% CI 85-95%). Analysis of the small subgroup of patients with chronic obstructive pulmonary disease showed that a mismatched X/Q scan was confirmed by V/Q scanning in 21 of 34 cases (62%; 95% CI 45-78%). CONCLUSION: This study shows that in the great majority of patients with clinically suspected acute pulmonary embolism combination of chest X-ray with perfusion scintigraphy reliably replaced ventilation/perfusion scintigraphy in defining (mis)-matching of segmental perfusion defects. These results need confirmation before the chest X-ray can fully obviate the use of ventilation scintigraphy.

Adult↗

Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. A comparison with pulmonary angiography.

STUDY OBJECTIVE: To assess the accuracy of a rapid ELISA D-dimer assay for the exclusion of pulmonary embolism (PE) in patients suspected of PE, using pulmonary angiography alone as reference method rather than a diagnostic strategy including lung scintigraphy and leg vein ultrasonography. METHODS: In 342 patients who were examined by pulmonary angiography to diagnose or exclude PE, the accuracy of the quantitative rapid VIDAS D-dimer test for the exclusion of PE was evaluated retrospectively. D-dimer levels were assayed in frozen samples collected during the diagnostic work-up at the time of pulmonary angiography while on treatment with unfractionated heparin for 1-2 days. RESULTS: Mean plasma D-dimer concentrations were increased in patients with angiographic evidence of PE (P <0.0001). The sensitivity of D-dimer for segmental PE was 98%, its accuracy in excluding segmental PE was 99%, higher than the respective figures for subsegmental PE (76% and 94%; P <0.01, both). For both forms of PE combined the sensitivity was 90% and the negative predictive value 94%. DISCUSSION: The sensitivity and negative predictive values reported here, are low compared with previous studies using the same rapid ELISA D-dimer assay. This probably reflects an overlooking of mild cases of subsegmental PE in previous studies, although a reduction of D-dimer levels by the heparin pretreatment may have contributed to part of the discrepancy. Prospective studies are needed to clarify this issue.

Adult↗

The value of pulmonary angiography for the differential diagnosis of pulmonary embolism.

The aim this study was to evaluate potential additional information of pulmonary angiography in patients with suspected pulmonary embolism and non-diagnostic lung scan findings. In a series of 150 patients who underwent pulmonary angiography for suspected venous thromboembolism, the images for potential alternative diagnoses other than pulmonary embolism were evaluated. All patients had non-diagnostic lung scan findings. Angiography was performed both by conventional and by digital subtraction angiography techniques. Images were evaluated by at least two experienced readers. Angiograms were scored for both presence or absence of pulmonary embolism, as well as other diagnoses. Pulmonary embolism was proven in 40 patients (27 %) and excluded in 105 patients (70 %), whereas non-interpretable images were obtained in 5 patients (3 %). A range of alternative diagnoses were detected by angiography: atelectasis (n = 24), pleural effusion (n = 15), pneumonia (n = 11), emphysematous bullae (n = 8), neoplasm (n = 3), atrial septum defect (n = 2), chronic thromboembolism (n = 1), and other diagnoses (n = 3). Overall, only 54 patients (36 %) had completely normal angiograms. Although pulmonary angiography remains the reference method for the diagnosis of pulmonary embolism, one has to be aware of other, often unexpected, but equally important findings which could influence the management of the patient. This aspect of pulmonary angiography has been insufficiently emphasized in the literature.

Adult↗

Requirements for appropriate evaluation of diagnostic tests in suspected pulmonary embolism.

In contrast to the development of new drugs, strict guidelines for the development of new diagnostic methods do not exist. A diagnostic test can be made available without proper evaluation of its clinical utility, which can lead to its premature introduction and inappropriate use. In this review suggestions are made regarding the criteria that should be met during the various phases of development of new diagnostic techniques. It is suggested that a new diagnostic test should only be implemented in routine clinical use after all phases of development have been properly performed with good results. Several diagnostic tests for pulmonary embolism (pulmonary angiography, ventilation-perfusion scintigraphy, D-dimer assays, and spiral computed tomography), and the studies evaluating them, are thereafter reviewed. It is concluded that present pulmonary angiography and ventilation-perfusion scintigraphy are the only properly evaluated diagnostic tests for pulmonary embolism. Although new developments, such as D-dimer assays and the spiral computed tomographic scan are certainly promising, further studies are needed to determine their real value and safety in the diagnostic work-up of patients suspected of pulmonary embolism.

Angiography↗