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Biomedical subjects

F De Winter

Publications and source records attributed to F De Winter.

18 recordsLinked to original sources

Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative (131)I-lipiodol therapy.

The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before (131)I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial (131)I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after (131)I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after (131)I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in (131)I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life.

Aged↗

Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary?

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before (131)I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after (131)I-lipiodol ( n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry ( n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 ( n=17) or 4 ( n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity ( n=31) compared with 0.42%+/-0.20% in the non-KI group ( n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group ( n=19) versus 11.9+/-5.9 Gy in the non-KI group ( n=21). These differences were statistically significant ( P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident ( P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Carcinoma, Hepatocellular↗

Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in clinical infectious diseases.

18-F-fluoro-D-deoxyglucose positron emission tomography (FDG PET) has become an established imaging tool in clinical oncology, cardiology and neurology and is now entering the field of clinical infectious diseases. The purpose of this article is to review the currently available, albeit limited, literature on FDG PET in the diagnosis of various infections and fever of unknown origin. Those indications for which FDG PET offers added value over more available techniques like labelled leucocyte scanning, gallium scanning and magnetic resonance imaging are especially highlighted. FDG PET seems to have an incremental value in the assessment of chronic osteomyelitis, especially in the axial skeleton, as well as in the diagnostic workup of fever of unknown origin and HIV complications. Cost-effectiveness studies are needed to define its place in the current diagnostic strategies of these pathologies.

Fever of Unknown Origin↗

Injury-induced class 3 semaphorin expression in the rat spinal cord.

In this study we evaluate the expression of all members of the class 3 semaphorins and their receptor components following complete transection and contusion lesions of the adult rat spinal cord. Following both types of lesions the expression of all class 3 semaphorins is induced in fibroblast in the neural scar. The distribution of semaphorin-positive fibroblasts differs markedly in scars formed after transection or contusion lesion. In contusion lesions semaphorin expression is restricted to fibroblasts of the meningeal sheet surrounding the lesion, while after transection semaphorin-positive fibroblast penetrate deep into the center of the lesion. Two major descending spinal cord motor pathways, the cortico- and rubrospinal tract, continue to express receptor components for class 3 semaphorins following injury, rendering them potentially sensitive to scar-derived semaphorins. In line with this we observed that most descending spinal cord fibers were not able to penetrate the semaphorin positive portion of the neural scar formed at the lesion site. These results suggest that the full range of secreted semaphorins contributes to the inhibitory nature of the neural scar and thereby may inhibit successful regeneration in the injured spinal cord. Future studies will focus on the neutralization of class 3 semaphorins, in order to reveal whether this creates a more permissive environment for regeneration of injured spinal cord axons.

Animals↗

18FDG PET versus high-dose 67Ga scintigraphy for restaging and treatment follow-up of lymphoma patients.

To date, only one published study has directly compared 67Ga scintigraphy (low dose, planar) with planar dual-head gamma camera 18F-fluorodeoxyglucose (18FDG) imaging for the purpose of treatment follow-up monitoring in lymphoma patients, and no data on restaging are available. The present study reports the direct comparison of high-dose (297-370 MBq) 67Ga planar and single photon emission computed tomography (SPECT) imaging and conventional 18FDG positron emission tomography (PET) for restaging and treatment follow-up of lymphoma patients versus a gold standard consisting of morphological imaging, including plain radiography and computed tomography (CT) scanning, bone marrow examination and long-term follow-up (<12 months). Sixteen patients, 10 with non-Hodgkin's lymphoma and six with Hodgkin's disease, were included (10 men, six women; median age, 43 years; range, 16-64 years). The median follow-up time was 27 months (range, 12-34 months). In two patients, 67Ga and 18FDG PET (370 MBq) were performed twice, resulting in 18 cross-sectional episodes. In 11 episodes, the results obtained by both imaging modalities were in agreement with regard to the presence or absence of disease when compared with the gold standard. However, the abnormalities found on 18FDG PET were always more extensive. In two episodes, 67Ga imaging normalized after treatment, whereas PET showed significant regression followed by subsequent normalization. In four additional episodes, 67Ga images were negative, whereas 18FDG PET visualized non-tumour-related pathology, such as lung infection, rib fracture or dense thymic tissue. In one gold standard-negative patient, the underlying cause of sternal FDG uptake remained undetermined. The data presented, although limited in number, suggest that 18FDG PET performs better than Ga imaging in monitoring lymphoma disease status. However, a correlation with clinical history and a knowledge of the characteristics of benign lesions are mandatory. Further studies are recommended.

Adolescent↗

Biodistribution and dosimetry of 99mTc-ciprofloxacin, a promising agent for the diagnosis of bacterial infection.

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time-activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid, predominantly urinary excretion of 99mTc ciprofloxacin, with low to absent brain, lung and bone marrow uptake and low liver uptake and excretion. Accordingly, imaging conditions are excellent for both the thoracic and the abdominal region, even at early time points (60 min) post injection. In none of the volunteers was the gallbladder visualised. Approximately 60% of the injected activity was recovered in urine by 24 h post injection. The highest absorbed doses were received by the urinary bladder wall, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. The amount of 99mTc ciprofloxacin required for adequate planar and tomographic imaging results in an acceptable effective dose to the patient.

Adult↗

Age- and gender-specific differences in left ventricular cardiac function and volumes determined by gated SPET.

The aim of this study was to determine normative volumetric data and ejection fraction values derived from gated myocardial single-photon emission tomography (SPET) using the commercially available software algorithm QGS (quantitative gated SPET). From a prospective database of 876 consecutive patients who were referred for a 2-day stress-rest technetium-99m tetrofosmin (925 MBq) gated SPET study, 102 patients (43 men, 59 women) with a low (<10%) pre-test likelihood of coronary disease were included (mean age 57.6 years). For stress imaging, a bicycle protocol was used in 79 of the patients and a dipyridamole protocol in 23. Left ventricular ejection fraction (LVEF) and end-diastolic and -systolic volumes (EDV and ESV) were calculated by QGS. EDV and ESV were corrected for body surface area, indicated by EDVi and ESVi. To allow comparison with previous reports using other imaging modalities, men and women were divided into three age groups (<45 years, > or =45 years but <65 years and > or =65 years). Men showed significantly higher EDVi and ESVi values throughout and lower LVEF values when compared with women in the subgroup > or =65 years (P<0.05, ANOVA). Significant negative and positive correlations were found between age and EDVi and ESVi values for both women and men and between LVEF and age in women (Pearson P< or =0.01). LVEF values at bicycle stress were significantly higher than at rest (P=0.000, paired t test), which was the result of a significant decrease in ESV (P=0.003), a phenomenon which did not occur following dipyridamole stress (P=0.409). The data presented suggest that LVEF and EDVi and ESVi as assessed by QGS are strongly gender-specific. Although the physiological significance of these results is uncertain and needs further study, these findings demonstrate that the evaluation of cardiac function and volumes of patients by means of QGS should consider age- and gender-matched normative values.

Adult↗

The anti-tumoral activity of neoadjuvant intra-arterial 131I-lipiodol treatment for hepatocellular carcinoma: a pilot study.

BACKGROUND: The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol administration before liver transplantation. METHODS: In this preliminary, prospective study we treated 10 consecutive HCC patients by intra-arterial injection of 131I-lipiodol into the hepatic artery followed by liver transplantation within 1-9 months (mean 3.4). After hepatic catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51 mCi) was instilled as selective as possible, depending on the distribution of the tumors: non-selectively in the hepatic artery propria (n = 4), selectively in the right and/or left hepatic artery (n = 3) or super-selectively in segmental arteries (n = 3). RESULTS: Anti-tumoral activity was regarded as obvious with 1) a strong decrease of alfa-fetoprotein (AFP), comparing the highest recorded value before and after 131I-lipiodol and/or 2) a downstaging in TNM classification on the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors with > 50% necrosis on histo-pathology of the explanted liver, without previous chemoembolization. Either of these criteria were met by 5/10 (50%) of patients. A 4) downstaging in pTNM classification on histopathology compared to the TNM classification of the MRI and/or a 5) tumor necrosis of only 10-50% were regarded as possibly tumor-related but were not accepted as a single criteria of anti-tumoral activity. This was seen in 3/10 (30%) of patients. Clinical side-effects of the 131I-lipiodol therapy were generally mild with a temperature rise in two cases, nausea without vomiting in another two and upper back pain in one patient. In one patient progressive liver failure developed one week after 131I-lipiodol therapy necessitating premature liver transplantation after 4 weeks. CONCLUSION: With the use of stringent anti-tumoral criteria, this study shows evidence of an anti-tumoral effect in 50% of patients. Our data support the evaluation on larger patient numbers to confirm the promising anti-tumoral activity of 131I-lipiodol in HCC patients candidated for liver transplantation.

Aged↗

Cardiac fluorine-18 fluorodeoxyglucose imaging using a dual-head gamma camera with coincidence detection: a clinical pilot study.

Dual-headed gamma cameras with coincidence detection (MCD) are increasingly used for imaging of positron-emitting tracers, such as fluorine-18 fluorodeoxyglucose (FDG). In this study, we examined differences between FDG MCD and FDG positron emission tomography (PET) as the gold standard to determine whether FDG MCD could be used for assessment of myocardial viability in daily practice. Nineteen patients with a previous myocardial infarction (17 men; mean left ventricular ejection fraction 44%+/-13%) underwent FDG MCD, FDG PET, resting echocardiography and technetium-99m tetrofosmin gated single-photon emission tomography (SPET). At the 50% threshold value for FDG PET, the area under the receiver operating characteristic curve for FDG MCD was 0.77+/-0.03. In 107 dyssynergic segments on echocardiography and 151 segments with hypoperfusion on 99mTc-tetrofosmin SPET, the specificity of FDG MCD for the detection of myocardial viability was 72% and 76% respectively, with a sensitivity of 69% and 72% respectively. Regional analysis showed a significantly lower agreement of FDG MCD and FDG PET in the inferior and septal regions (58% for dyssynergic segments and 65% for segments with hypoperfusion), as compared with the other regions (85% for dyssynergic regions, P<0.05, and 86% for segments with hypoperfusion, P<0.05). Five patients (26%), who all had a body mass index > or =25% kg/m2, showed more than 25% disagreement between FDG MCD and FDG PET. Because of the moderate overall agreement with FDG PET, the low sensitivity in akinetic or dyskinetic regions and the low agreement in the inferior and septal regions, further studies and implementations of technical developments are needed before FDG MCD can be introduced into clinical practice for the assessment of myocardial viability.

Adult↗

Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS.

This study evaluates the expression of the chemorepellent semaphorin III (D)/collapsin-1 (sema III) following lesions to the rat CNS. Scar tissue, formed after penetrating injuries to the lateral olfactory tract (LOT), cortex, perforant pathway, and spinal cord, contained numerous spindle-shaped cells expressing high levels of sema III mRNA. The properties of these cells were investigated in detail in the lesioned LOT. Most sema III mRNA-positive cells were located in the core of the scar and expressed proteins characteristic for fibroblast-like cells. Neuropilin-1, a sema III receptor, was expressed in injured neurons with projections to the lesion site, in a subpopulation of scar-associated cells and in blood vessels around the scar. In contrast to lesions made in the mature CNS, LOT transection in neonates did not induce sema III mRNA expression within cells in the lesion and was followed by vigorous axonal regeneration. The concomitant expression of sema III and its receptor neuropilin-1 in the scar suggests that sema III/neuropilin-1-mediated mechanisms are involved in CNS scar formation. The expression of the secreted chemorepellent sema III following CNS injury provides the first evidence that chemorepulsive semaphorins may contribute to the inhibitory effects exerted by scars on the outgrowth of injured CNS neurites. The vigorous regrowth of injured axons in the absence of sema III following early neonatal lesions is consistent with this notion. The inactivation of sema III in scar tissue by either antibody perturbation or by genetic or pharmacological intervention could be a powerful means to promote long-distance regeneration in the adult CNS.

Animals↗

Evidence for a role of the chemorepellent semaphorin III and its receptor neuropilin-1 in the regeneration of primary olfactory axons.

To explore a role for chemorepulsive axon guidance mechanisms in the regeneration of primary olfactory axons, we examined the expression of the chemorepellent semaphorin III (sema III), its receptor neuropilin-1, and collapsin response mediator protein-2 (CRMP-2) during regeneration of the olfactory system. In the intact olfactory system, neuropilin-1 and CRMP-2 mRNA expression define a distinct population of olfactory receptor neurons, corresponding to immature (B-50/GAP-43-positive) and a subset of mature (olfactory marker protein-positive) neurons located in the lower half of the olfactory epithelium. Sema III mRNA is expressed in pial sheet cells and in second-order olfactory neurons that are the target cells of neuropilin-1-positive primary olfactory axons. These data suggest that in the intact olfactory bulb sema III creates a molecular barrier, which helps restrict ingrowing olfactory axons to the nerve and glomerular layers of the bulb. Both axotomy of the primary olfactory nerve and bulbectomy induce the formation of new olfactory receptor neurons expressing neuropilin-1 and CRMP-2 mRNA. After axotomy, sema III mRNA is transiently induced in cells at the site of the lesion. These cells align regenerating bundles of olfactory axons. In contrast to the transient appearance of sema III-positive cells at the lesion site after axotomy, sema III-positive cells increase progressively after bulbectomy, apparently preventing regenerating neuropilin-1-positive nerve bundles from growing deeper into the lesion area. The presence of sema III in scar tissue and the concomitant expression of its receptor neuropilin-1 on regenerating olfactory axons suggests that semaphorin-mediated chemorepulsive signal transduction may contribute to the regenerative failure of these axons after bulbectomy.

Age Factors↗

Expression and characterization of molluscan insulin-related peptide VII from the mollusc Lymnaea stagnalis.

A complementary DNA clone encoding molluscan insulin-related peptide VII was identified from a complementary DNA library of the cerebral ganglia of the CNS of the freshwater snail, Lymnaea stagnalis. The novel molluscan insulin-related peptide VII complementary DNA encodes a preprohormone resembling the organization of preproinsulin, with a putative signal sequence, and an A and B chain, and is connected by an unusual long C peptide. The A and B chains, as well as the C peptide of molluscan insulin-related peptide VII, differ remarkably in primary structure with the previously identified molluscan insulin-related peptides. The C peptide of molluscan insulin-related peptide VII shares no significant sequence identity with counterparts in other molluscan insulin-related peptides. Both molluscan insulin-related peptide VII and the other molluscan insulin-related peptides exhibit structural features which make them a unique class of the insulin superfamily. Molluscan insulin-related peptide VII complementary DNA was shown to hybridize in situ with messenger RNA present in the cerebral light green cells, neuroendocrine cells that control growth and that have previously been shown to produce molluscan insulin-related peptides I-III and V. Uniquely, the molluscan insulin-related peptide VII gene is also expressed in neurons that may form part of the feeding circuitry in Lymnaea, indicating that it may function as a neurotransmitter/neuromodulator.

Amino Acid Sequence↗

An infected hip prosthesis in a dog diagnosed with a 99mTc-ciprofloxacin (infecton) scan.

This case report describes the use of the 99mTc-labeled radiopharmaceutical ciprofloxacin (Infecton) in a case of hip prosthesis loosening in a dog. Serial planar radiographs were not conclusive, and culture of the synovial fluid was negative. Antibiotic treatment did not result in improvement of the lameness. Scintigraphy was performed with 99-Tc-Infecton, a tracer claimed to be specific for infection. Antibiotic treatment was interrupted 6 weeks prior to the examination. Planar and tomographic images at 3 h and at 24 h postinjection showed increased activity along the acetabulum and the proximal femoral bone surrounding the femoral prosthesis, indicating focal infection. Bacteriology performed after removal of the implant revealed Pseudomonas aeruginosa.

Animals↗