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Biomedical subjects

E K Pauwels

Publications and source records attributed to E K Pauwels.

At least 19 recordsLinked to original sources

Biodistribution of lymphokine-activated killer (LAK) cells in Wag rats after hepatic-artery or jugular-vein infusion.

This study deals with the biodistribution of syngeneic radiolabeled lymphokine-activated killer (LAK) cells in Wag rats after infusion via the hepatic artery or the jugular vein. The biodistribution of 111Indium-labeled LAK cells was evaluated using serial whole-body gamma camera imaging. Furthermore, we investigated 2 factors that might influence the biodistribution of these effector cells: purity of LAK cells and administration of interleukin-2 (IL-2). After injection of 111Indium-labeled LAK cells via the hepatic artery or via the jugular vein we could detect important differences in the biodistribution pattern up to 5 hr after injection. LAK cells administered via the jugular vein were all found in the lungs up to 2 hr after injection and then redistributed to the liver and to the spleen. LAK cells administered via the hepatic artery were all found in the liver after injection and redistributed after 2 hr mainly to the spleen. About 8 hr after injection we could no longer detect any differences in the biodistribution pattern according to the route of administration. Biodistribution was followed for up to 72 hr after injection but the pattern showed no change after 8 hr, whichever the route of administration. A purified adherent-LAK population, a large granular lymphocyte culture with only 6% T cells, showed the same distribution pattern as standard LAK cells (40% T cells). Infusions of 40,000 units of IL-2 per day, starting 3 days before and continuing after administration of radio-labeled LAK cells, accelerated the redistribution of these cells by both routes of administration. We conclude that up to 2 hr after local infusion, a high concentration of LAK cells in the first capillary bed can be obtained. Therefore, local administration of LAK cells may be more effective against tumors.

Animals

Quantitative analysis in single photon emission tomography (SPET).

Quantitative analysis can improve the sensitivity and specificity of single photon emission tomography (SPET) procedures, as well as reduce inter- and intraobserver variabilities. Quantification of the radioactivity distribution is the ultimate goal of SPET. In this review we consider the basic requirements for an optimum three-dimensional reconstruction of the radionuclide distribution to enable quantification. Attenuation and scatter correction as well as varying resolution are the major problems. In the older SPET systems quantification was hampered by the lack of system sensitivity and sufficient computer power. Therefore, the imaging system was often assumed to be shift invariant and linear and the attenuation throughout the object uniform. More sophisticated solutions have been proposed and with more or less success implemented, but not for application in daily practice. Knowledge (measurement) of the attenuation is often required. New generation SPET systems employing multi-detectors and super minicomputers will ease the implementation of these solutions.

Humans

The clinical impact of thallium-201 reinjection scintigraphy for detection of myocardial viability.

In a clinical study, the value of thallium-201 reinjection was studied in 139 patients with suspected or known coronary artery disease who showed one or more persistent defects after conventional stress-redistribution imaging. Fifty-nine (42%) patients had sustained a Q-wave myocardial infarction. Sixty-eight (49%) patients showed a reversible defect in at least one myocardial segment at redistribution, while 71 (51%) had persistent defects only. Following reinjection additional segmental filling-in was seen in 95 (68%) patients, including 50 of the 68 (74%) patients with reversible defects and 45 of the 71 (63%) with persistent defects only. On the immediately post-exercise images, 458 (47%) of 973 segments showed perfusion defects. At redistribution 105 (23%) of the 458 defects showed filling-in, whereas of the remaining 353 persistent defects 164 (46%) resolved additionally after reinjection. Thirteen (10%) of 133 Q-wave related defects showed filling-in at redistribution compared with 22 (27%) of 82 remote defects (P = 0.001). After reinjection additional filling-in of defects was seen in 47 (39%) of 120 Q-wave related defects compared with 35 (58%) or 60 remote defects (P = 0.015). Overall, 60 (45%) of 133 Q-wave related defects resolved compared with 57 (70%) of 82 remote defects (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease

Combined assessment of technetium-99m SESTAMIBI planar myocardial perfusion images at rest and during exercise with rest/exercise left ventricular wall motion studies evaluated from gated myocardial perfusion studies.

The favorable physical characteristics of technetium-99m-labeled 2-methoxy-2-methylisopropyl-1-isonitril (Tc-SESTAMIBI) enable the combined evaluation of both myocardial perfusion and left ventricular wall motion. To assess the potential of rest and exercise regional myocardial function as an adjunct to planar myocardial perfusion imaging, 60 patients with coronary artery disease and documented arteriographic findings were studied with both protocols during a single study. Exact segmental concordance between myocardial perfusion and wall motion studies was 77% (701/900 segments). Overall sensitivity and specificity to detect hemodynamically significant coronary artery disease with Tc-SESTAMIBI myocardial perfusion imaging were 89% and 79%, respectively, with resting wall motion studies 83% and 71%, respectively, and with rest/exercise wall motion studies, 85% and 71%, respectively. If the results of both perfusion and rest/exercise studies were combined, sensitivity increased to 96% and specificity decreased to 64%. The differences with perfusion studies alone were not statistically significant. Thus despite a good correlation between regional left ventricular function and perfusion, no statistically significant incremental diagnostic value was found when the results of both perfusion and wall motion studies were combined.

Adult

4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

Animals

The use of bisphosphonates in the treatment of osteoporosis.

The efficacy of bisphosphonates in the treatment of conditions characterized by increased osteoclastic bone resorption has been established. Recent evidence indicates that these compounds are also effective in the treatment of patients with osteoporosis. Two main protocols have been tried. One is based on the intermittent administration of the bisphosphonate, which is expected to decrease bone resorption, and give a drug-free period during which bone formation may proceed at a normal rate, leading to a positive calcium balance. The other argues that the resetting of the equilibrium in a cyclical process is, as a rule, incomplete and continuous low-grade suppression of resorption will result in a continuing positive bone balance. Intermittent administration of the first generation bisphosphonate, etidronate, for up to three years increases trabecular bone density, stabilizes it after two years, and appears to reduce the rate of new vertebral fractures in women with postmenopausal osteoporosis. Longer follow-up studies are needed before this beneficial effect is unequivocally established. Continuous administration of the second-generation bisphosphonate, pamidronate, increases spinal bone density in patients with osteoporosis linearly for up to four years, and is associated with a low rate of new vertebral fractures. These results need to be confirmed in controlled studies involving more patients. There are indications that pamidronate given continuously can prevent glucocorticoid-induced bone loss. There is no information about the effects of bisphosphonates on non-vertebral fractures. There are limited data about the use of bisphosphonates in the prevention of postmenopausal bone loss. Extensive studies on efficacy and safety are needed before this treatment is offered as an alternative to hormone replacement therapy.

Bone Resorption

MRI screening of kindred at risk of developing paragangliomas: support for genomic imprinting in hereditary glomus tumours.

Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing. In eight previously diagnosed members, eight known glomus tumours of which one functioning, and two unknown glomus tumours and one unknown pheochromocytoma were present. Six unsuspected members showed ten glomus tumours and one pheochromocytoma. It has been suggested that the manifestation of hereditary glomus tumours is determined by the sex of the transmitting parent. There were no tumours in the descendants of female gene carriers. Comparing the likelihood of inheritance with genomic imprinting versus inheritance without genomic imprinting we found an odds ratio of 23375 in favour of genomic imprinting.

Carotid Body

Does haemodialysis impair macrophage Fc receptor function?

Patients treated with chronic haemodialysis are at risk of infections, possibly because of impaired function of macrophage Fc receptors. Using [123I]-labelled aggregates of human IgG ([123I]-AIgG) as a probe of Fc-receptor-mediated function, we examined eight patients treated with chronic intermittent haemodialysis (HD), eight patients treated with CAPD, eight patients with preterminal renal failure who had not yet received renal replacement therapy, and eight healthy controls. In all three patient groups the first elimination half-life of [123I]-AIgG was decreased, suggesting accelerated binding of the probe. In the HD group overall clearance of [123I]-AIgG was similar to the value found in healthy controls. In the CAPD and preterminal renal failure group clearance was decreased as compared with the HD patients. Uptake of [123I]-AIgG by liver and spleen was quantitatively similar in patients and controls, but hepatic uptake of [123I]-AIgG reached its maximum earlier in the patients treated with HD. These results suggest that Fc receptor function is not impaired in patients who undergo chronic haemodialysis.

Adult

Clinical significance of silent ischaemia and implications for treatment: role of radionuclide techniques.

Radionuclide techniques have added substantial information to aid detection and heighten the clinical significance of silent ischaemia. While non-invasive assessment of myocardial perfusion, metabolism and wall motion have increased the knowledge of the pathophysiology of silent ischaemia, radioisotope techniques may provide information far beyond that obtained by electrocardiographic criteria alone. Whether patients with silent ischaemia should be treated can only be inferred from indirect evidence suggested by preliminary trials. Only randomized, controlled, clinical trials will yield the definite answers as to the effects of treatment on clinical outcome.

Angina Pectoris

Deficiency of complement component C3 is associated with accelerated removal of soluble 123I-labelled aggregates of IgG from the circulation.

Complement and erythrocyte complement receptors CR1 (CD35) play an important role in the clearance of immune complexes. We studied the elimination of soluble 123I-labelled aggregates of human immunoglobulin G (123I-AIgG), used as a model for immune complexes, in two patients with a congenital and two patients with an acquired deficiency of complement component C3, and compared these with 10 healthy controls. The first disappearance halflife of 123I-AIgG was shorter (3.3 +/- 0.4 versus 7.0 +/- 0.4 min in the controls, P = 0.005) and maximal hepatic uptake of aggregates was increased in the C3 deficient patients (maximal liver/background ratio 3.6 +/- 0.4 versus 2.7 +/- 0.2 in controls, P = 0.04). Apparently, in the absence of C3, removal of circulating immune complexes by the liver is accelerated, probably through Fc receptor-dependent mechanisms.

Adult

Assessment of acute myocardial infarction by nuclear imaging techniques.

In recent years, nuclear cardiology techniques have been successfully applied in patients with acute myocardial infarction. These scintigraphic measurements have provided important diagnostic, therapeutic, and prognostic information based on the extent of myocardial damage and the functional reserve of the left ventricle. In particular, in the thrombolytic era, myocardial perfusion imaging and radionuclide angiography have been shown to be valuable methods for studying the effects of reperfusion on the extent of myocardial damage. Nuclear magnetic resonance imaging, preferably with contrast enhancement, is one of the newly developed nuclear imaging techniques that have probably the greatest potential in accurately delineating myocardial infarct size and in evaluating left ventricular function. Radionuclide procedures, on the other hand, employ more biologically oriented tracers and are therefore capable of monitoring biochemical changes in the course of acute myocardial infarction.

Antibodies, Monoclonal

A five day course of high dose corticosteroids has no effect on the clearance of soluble aggregates of human immunoglobulin G in healthy volunteers.

It is thought that glucocorticosteroids impair the clearance of immune complexes by the mononuclear phagocyte system (MPS). We studied the effect of a five day course of prednisone (1 mg/kg body weight per day) on MPS function in 10 healthy volunteers, using soluble radiolabeled aggregates of human immunoglobulin G as a probe. MPS function was assessed before steroid treatment, and again 24 hours after the last dose of prednisone. Elimination kinetics and the uptake of the immunoglobulin aggregates by liver and spleen did not change after prednisone treatment. This suggests that, in contrast to general belief, high doses of glucocorticosteroids have no direct, acute effect on MPS function.

Adrenal Cortex Hormones

Evaluation of the incremental diagnostic value and impact on patient treatment of thallium scintigraphy.

The incremental diagnostic yield of exercise 201Tl scintigraphy with visual and quantitative analysis was determined in 191 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was used as the gold standard. After pre-test clinical and exercise electrocardiographic data were taken into consideration, scintigraphy was found to have additional diagnostic value both in the diagnosis of CAD and of multivessel disease, with quantitative analysis being superior to visual analysis. The impact of 201Tl scintigraphy on the patient's treatment--conservative treatment versus revascularization--was also evaluated. The impact was relatively low, as the decision for revascularization was based primarily on the angiographic result and the severity of the anginal pain. This result reflects only the decision making process used in our clinic and permits no conclusion to be made concerning the possible value of 201Tl scintigraphy in this type of medical decision making process.

Coronary Angiography

99mTc human immunoglobulin scintigraphy--a reliable method to detect joint activity in rheumatoid arthritis.

The ability of 99mtechnetium labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in 30 patients with rheumatoid arthritis (RA). All patients were injected with 350 MBq 99mTc-IgG and imaging was performed 4 h later. This resulted in excellent images of inflamed synovium. Scores for 99mTc-IgG joint scintigraphy correlated highly with scores for joint swelling and C-reactive protein levels, weakly with pain scores and not with radiographic scores of joint destruction. These results suggest that 99mTc-IgG joint scintigraphy may provide an objective test to detect synovitis and measure the activity of the disease.

Adult

Alternative stress methods for the diagnosis of coronary artery disease.

Bicycle exercise and treadmill exercise are the commonest devices used in the evaluation of coronary artery disease. However, not all patients are capable of performing a maximal exercise test due to orthopaedic, vascular or pulmonary disease, poor physical condition and motivation. Alternative tests as a reliable substitute for the more conventional methods have been proposed, such as right atrial pacing, arm ergometry, handgrip test, cold pressure test, and inotropic stimulation. In particular, pharmacological stress testing with dipyridamole (and recently with adenosine and dobutamine) in combination with radionuclide techniques has gained much interest. This review will consider the usefulness and role of alternative stress testing to provoke myocardial ischaemia, with emphasis on pharmacological stress testing in conjunction with thallium-201 myocardial perfusion scintigraphy.

Adenosine

A prospective comparison of 99mTc-labeled polyclonal human immunoglobulin and 111In granulocytes for localization of inflammatory bowel disease.

There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with 99mTc was compared with that of 111In granulocytes. To determine the specificity of 99mTc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. 99mTc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intense accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with 111In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive 99mTc-IgG scintigraphy (6 versus 12 with 111In granulocytes). In view of the low sensitivity and specificity, it is concluded that 99mTc-IgG is not suitable for the scintigraphic staging of IBD patients.

Adolescent