[The biopsying of at least 5 mediastinal lymph node stations for presurgical staging in patients with a non-small-cell lung carcinoma].
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Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
W J Oyen
Publications and source records attributed to W J Oyen.
[Diagnostic image (149). A woman with a mass at the base of the tongue. Lingual thyroid].
A 48-year-old woman had a lump in her throat and dysphagia. On examination an oropharyngeal mass was seen which was diagnosed as a lingual thyroid.
Choristoma↗
Tc-99m-labeled C5a and C5a des Arg74 for infection imaging.
UNLABELLED: The complement anaphylatoxin C5a and its natural metabolite C5a des Arg(74) (C5adR) are involved in several stages of the inflammatory process. Both act on a common receptor expressed on different cell types, including neutrophils and monocytes. The receptor binding affinity of C5a is in the nanomolar range and exceeds that of C5adR by 1-2 orders of magnitude. The biologic potency of C5a is considerably higher than that of C5adR. Here we tested both proteins labeled with (99m)Tc for imaging of infection. METHODS: The proteins were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator. The preparations were tested for imaging of infection in a rabbit model of intramuscular infection. Biodistribution of the radiolabel was determined by gamma-camera imaging and by counting dissected tissues at 5 h p.i. RESULTS: C5a and C5adR showed in vivo abscess uptakes of 0.12 and 0.025%ID/g, abscess/muscle ratios of 76 and 14, abscess/blood ratios of 9.1 and 2.6, and ROI derived target-to-background ratios of 5.9 and 2.1, respectively at 5 h p.i. CONCLUSION: For infection imaging (99m)Tc-labeled C5a showed excellent in vivo characteristics. However, C5a is a very bioactive protein, impeding its clinical use as an infection imaging agent. The naturally occurring partial agonist C5adR has less biological effect but showed suboptimal imaging characteristics. The present study showed that for adequate localization of a receptor binding ligand affinities for the receptor in the nanomolar range are required.
Animals↗
Stimulation of growth-hormone release with clonidine does not distinguish individual cases of idiopathic Parkinson's disease from those with striatonigral degeneration.
Multiple System Atrophy (MSA) and idiopathic Parkinson's disease (PD) can be difficult to distinguish. There is an ongoing debate about the diagnostic value of the growth-hormone response to clonidine (CGH-test) in PD and MSA. We investigated whether the CGH-test can identify individual patients in the early stages of PD (n = 21) and Striatonigral Degeneration (SND, n = 11), a particular variety of MSA. Patients were diagnosed on the basis of clinical criteria and IBZM-SPECT. Clonidine induced a greater total serum growth-hormone production in PD than in SND (p = 0.01). However, taking the difference in prevalence of PD and SND into account, and because of the low likelihood ratios of the test, an increase of GH after clonidine increases the pre-test probability for PD by about only 5 %, while an absent response of GH also increases the pre-test probability for SND by about 5 %. We conclude that the CGH-test discriminates between groups of patients with PD and SND, but has little practical diagnostic value for identifying individual patients.
Aged↗
Evaluation of (pre-)malignant colonic abnormalities: endoscopic validation of FDG-PET findings.
The diagnostic accuracy of 2-[(18)F]-fluoro-2-deoxy- D-glucose positron emission tomography (FDG-PET) for the detection of (pre-)malignant lesions of the colon was compared with that of endoscopy. We selected a cohort of 39 patients [13 females and 26 males; mean age 62.3 years standard deviation (SD) 9.6 years] who underwent both FDG-PET and endoscopy (total of 44 procedures) in a 2-year period with a maximum interval between the examinations of 3 months (mean 30 days, SD 28 days). The underlying pathology was colorectal malignancies (24 patients), other malignancies (nine patients) and other disorders (six patients). Follow-up of resected colorectal cancer was the most common reason for the performance of endoscopy. In 19 patients FDG bowel uptake was interpreted as non-physiological, and in 18 patients abnormal findings (adenomatous polyps >3 mm or carcinoma) were detected by endoscopy. Compared with colonoscopy, FDG-PET had a sensitivity of 74% and specificity of 84%. The positive predictive value of FDG-PET was 78%. FDG-PET failed to detect small (diameter 3-10 mm) polyps in four patients. In nine cases abnormal FDG accumulation on PET imaging was the sole reason for performance of an endoscopic procedure. In these cases, endoscopy detected large adenomatous polyps in four patients and carcinomas in two patients, but no abnormalities were detected on endoscopy in the other three patients. There was a good correlation between the location of FDG uptake and endoscopy-positive lesions. FDG-PET is able to detect clinically relevant lesions of the colon. Our study suggests that it can be regarded as a useful adjunct in the non-invasive follow-up of patients with colorectal carcinomas.
Adenoma↗
Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase.
Various pathologic conditions, such as hemorrhage, hemolysis and cell injury, are characterized by the release of large amounts of heme. Recently, it was demonstrated that heme oxygenase (HO), the heme-degrading enzyme, and heme are able to modulate adhesion molecule expression in vitro. In the present study, the effects of heme and HO on inflammation in mice were analyzed by monitoring the biodistribution of radiolabeled liposomes and leukocytes in conjunction with immunohistochemistry. Small liposomes accumulate in inflamed tissues by diffusion because of locally enhanced vascular permeability, whereas leukocytes actively migrate into inflammatory areas through specific adhesive interactions with the endothelium and chemotaxis. Exposure to heme resulted in a dramatic increase in liposome accumulation in the pancreas, but also intestines, liver, and spleen exhibited significantly increased vascular permeability. Similarly, intravenously administered heme caused an enhanced influx of radiolabeled leukocytes into these organs. Immunohistochemical analysis showed differential up-regulation of the adhesion molecules ICAM-1, P-selectin, and fibronectin in liver and pancreas in heme-treated animals. Heme-induced adhesive properties were accompanied by a massive influx of granulocytes into these inflamed tissues, suggesting an important contribution to the pathogenesis of inflammatory processes. Moreover, inhibition of HO activity exacerbated heme-induced granulocyte infiltration. Here it is demonstrated for the first time that heme induces increased vascular permeability, adhesion molecule expression, and leukocyte recruitment in vivo, whereas HO antagonizes heme-induced inflammation possibly through the down-modulation of adhesion molecules.
Animals↗
Microscopic localization of PEG-liposomes in a rat model of focal infection.
In the present study the microscopic localization of polyethylene glycol (PEG) liposomes in infected tissues was studied with both light microscopy (LM) and transmission electron microscopy (TEM) in rats with focal intramuscular Staphylococcus aureus infection. PEG-liposomes containing colloidal gold were prepared and injected intravenously in rats with focal S. aureus infection and tissues were dissected at 24 h post injection. Sections were cut and liposomes were visualized for microscopic evaluation using silver enhancement. Uptake of PEG-liposomes was visualized by both scintigraphy and LM in the abscess, liver and spleen. In the infected area, the liposomes were mainly found in the vicinity of blood vessels. TEM showed that the liposomes were localized in the macrophages and to a lesser extent in endothelial cells in the infectious tissue. In the liver, the liposomes appeared mainly localized in Kupffer cells. In the spleen, uptake was only seen in cells of the red pulp and in cells around the central arteries. Our microscopic observations indicate that uptake and retention of PEG-liposomes in the infectious focus is a result of enhanced extravasation due to increased vascular permeability and subsequent phagocytosis of PEG-liposomes by macrophages in the infected tissue.
Abscess↗
Effect of subtotal colectomy on gastric emptying of a solid meal in slow-transit constipation.
BACKGROUND: Idiopathic slow-transit constipation is considered a panenteral disease in which patients may have delayed gastric emptying. The effects of total abdominal colectomy and ileorectal anastomosis on upper gut motility are unknown. The aim of this study was to evaluate gastric emptying in patients with idiopathic slow-transit constipation before and after subtotal colectomy. METHODS: Gastric emptying of a solid meal was studied by scintigraphic technique in 11 patients with idiopathic slow-transit constipation. The total colonic transit time was more than 72 hours in all patients studied, with delay in transit in all segments of the colon. The gastric emptying test was repeated 3 to 6 months after total abdominal colectomy and ileorectal anastomosis in ten of these patients. Before and after surgery, patients filled out a questionnaire to record upper gut symptoms. RESULTS: Solid gastric emptying was delayed (T1/2 > upper limit of normal) in 7 of 11 patients with idiopathic slow-transit constipation. Gastric emptying T1/2 was almost similar before and after surgery. Mean +/- standard deviation was 142 +/- 91 minutes before surgery and 146 +/- 67 minutes after surgery. Symptoms of vomiting and belching improved significantly after surgery. Symptoms of nausea, bloating, and pyrosis also decreased, but these changes failed to reach statistical significance. CONCLUSION: Despite a reduction in upper gut symptoms, total abdominal colectomy and ileorectal anastomosis does not improve delayed gastric emptying in patients with idiopathic slow-transit constipation.
Adult↗
Radiopharmaceuticals for scintigraphic imaging of infection and inflammation.
Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. Nowadays, a few radiopharmaceuticals are available that could replace radiolabeled leukocytes, such as: 67Ga-citrate, 99mTc-IgG and 99mTc-labeled antigranulocyte antibody preparations. Furthermore, various agents labeled with 99mTc are currently developed for this application: chemotactic peptides, cytokines and liposomes. Here, the characteristics and the diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.
Antibodies↗
Imaging infection/inflammation in the new millennium.
In the closing half of the past century a wide variety of approaches were developed to visualise infection and inflammation by gamma scintigraphy. Use of autologous leucocytes, labelled with indium-111 or technetium-99m, is still considered the "gold standard" nuclear medicine technique for the imaging of infection and inflammation. However, the range of radiopharmaceuticals used to investigate infectious and non-microbial inflammatory disorders is expanding rapidly. Developments in protein/peptide chemistry and in radiochemistry should lead to agents with very high specific activities. Recently, positron emission tomography with fluorine-18 fluorodeoxyglucose has been shown to delineate infectious and inflammatory foci with high sensitivity. The third millennium will witness a gradual shift from basic (non-specific) or cumbersome, even hazardous techniques (radiolabelled leucocytes) to more sophisticated approaches. Here a survey is presented of the different approaches in use or under investigation.
Animals↗
Radioimmunotherapy of B-cell non-Hodgkin's lymphoma.
In the past decade, several new antibody-based therapies - using either radiolabelled or unlabelled monoclonal antibodies - have become available for the treatment of patients with refractory or recurrent non-Hodgkin's lymphoma (NHL). Unlabelled monoclonal antibodies (mAbs) kill lymphoma cells by activating host immune effector mechanisms, or by inducing apoptosis. These mAbs can also be used to guide radionuclides to the lymphoma. This radioimmunotherapy (RIT) has been studied with various nuclides (131I, 90Y, 67Cu and 186Re) and with various mAbs. In this review the radionuclides, methods of dosing and recent RIT studies in patients with B-cell NHL are reviewed. Most of these studies demonstrate that RIT is an effective new treatment modality for NHL.
Antibodies, Monoclonal↗
Between the Scylla and Charybdis of peptide radionuclide therapy: hitting the tumor and saving the kidney.
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Humans↗
Distal femoral bone mineral density after total knee arthroplasty: a comparison with general bone mineral density.
The bone mineral density (BMD) of the distal femur may decrease after cemented total knee arthroplasty (TKA) as a result of the stress shielding effect of the femoral component. The purpose of the study was to determine the changes in BMD of the distal femur compared with those of the femoral necks and the lumbar spine after cemented TKA. BMD of two regions of interest in the distal femur, both femoral necks and the lumbar spine was measured with dual-energy X-ray absorptiometry in 10 patients (age range 41-80 years, mean 62 years) with 12 TKAs preoperatively and during follow-up for 1 year after surgery. The hip and spine measurements were performed for comparison to assess if general changes in BMD occurred after TKA. The median decrease in BMD in the region behind the anterior flange of the femoral component was 22% (95% CI: 12%-33%), while the average decrease in the region just above the femoral component was 8% (95% CI: 2%-13%). The difference in change of BMD between both regions before and 1 year after TKA was significant (p = 0.03). We found less than 1% difference in BMD of both femoral necks and the lumbar spine on average between the preoperative and 1 year follow-up measurements (not significant). A significant periprosthetic distal femoral bone resorption occurred after TKA. BMD of the femoral necks and lumbar spine did not differ 1 year after TKA.
Aged↗
Animal models of infection and inflammation and their role in experimental nuclear medicine.
In this review, basic aspects of nuclear medicine are described. One of the fields of research in nuclear medicine is the development of new radiopharmaceuticals for imaging infection and inflammation in humans. For this development, animal models are identified and modified to needs of a particular research question. In this review, a wide variety of models that are available in our laboratory are presented and the strengths and pitfalls are discussed.
Animals↗
The effect of molecular weight on nonspecific accumulation of (99m)T-labeled proteins in inflammatory foci.
UNLABELLED: Although several proteins have been proposed and tested for scintigraphic detection of infection, the most optimal characteristics of a protein for this application have not yet been determined. Molecular weight (MW) of the protein, its charge, shape, carbohydrate content, characteristics of the radionuclide and receptor interactions are factors that could affect the in vivo behavior of the infection imaging agent. The effect of molecular weight on nonspecific accumulation of (99m)Tc-labeled proteins in inflammatory foci was studied in a rat model. METHODS: Eleven proteins whose MWs ranged from 2.5 kDa up to 800 kDa were labeled with (99m)Tc using the hydrazinonicotinamide (HYNIC) chelator. Rats with S. aureus infection were injected i.v. with 15 MBq (99m)Tc-labeled protein. Gamma camera images were acquired and biodistribution of the radiolabel was determined ex vivo. RESULTS: From biodistribution data no significant correlation was found between abscess uptake and molecular size of the (99m)Tc-labeled proteins that were studied. Fast blood clearance with predominant uptake in liver and spleen was found for the largest proteins (MW 669 kDa-800 kDA). For proteins of intermediate size (MW 66 kDa -206 kDa) we found relatively slow blood clearance with relatively moderate uptake in liver and spleen. For smaller proteins (MW 2.5 kDa -29 kDa) rapid blood clearance with predominant kidney uptake was observed. The abscess uptake of the (99m)Tc-labeled proteins (%ID/g, 24 h p.i.) was highest for serum proteins IgG and BSA. Abscess uptake correlated well with blood levels: r = 0.95 and 0.84 at 4 and 24 h respectively (P < 0.005). The abscess-to-muscle ratios varied from 2.1 to 17.8 at 24 h p.i. with highest values for alpha-2 macroglobulin (MW 725 kDa) and the intermediate sized proteins (MW 66-206 kDa). Gamma camera imaging showed localization of all radiotracers at the site of infection with abscess-to-background ratios (A/B) ranging from 1.4 to 7.0 (IgG) at 20 h p.i. The serum proteins IgG and BSA showed highest blood levels and best infection imaging characteristics. CONCLUSION: Not molecular weight but blood residence time is the principal factor that determines localization of a nonspecific tracer protein in infectious foci. The ideal nonspecific infection imaging agent is a protein with a long circulatory half-life. From the proteins tested here IgG and albumin showed the best characteristics for an infection imaging agent.
Animals↗
Radiopharmaceuticals to image infection and inflammation.
Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, the preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. A few radiopharmaceuticals are available that could be used instead of radiolabeled leukocytes to scintigraphically visualize infectious and inflammatory foci, such as 67Ga-citrate and 99mTc-labeled antigranulocyte antibody preparations. Various agents labeled with 99mTc are currently developed for this application. Most of these newly developed agents are ligands that bind receptors on white blood cell subpopulations, ie, monoclonal antibodies, chemotactic peptides, and cytokines. Furthermore, agents are developed that potentially could distinguish between infection and nonmicrobial inflammation. In addition, 18F-fluorodeoxyglucose positron emission tomography imaging was proposed to visualize inflammatory foci when a high spatial resolution is required. In this article, the characteristics and diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.
Animals↗
In vivo efficacy of trovafloxacin against Bacteroides fragilis in mixed infection with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium in an established-abscess murine model.
The pharmacodynamic and pharmacokinetic properties of trovafloxacin were studied in a standardized murine model of established subcutaneous abscesses. Daily dosing regimens of 37.5 to 300 mg/kg every 8 h (q8h) or every 24 h (q24h) were started 3 days after inoculation with mixtures containing either Bacteroides fragilis-Escherichia coli-autoclaved cecal contents (ACC) or B. fragilis-vancomycin-resistant Enterococcus faecium (VREF)-ACC. Treatment was continued for 3 or 5 days. The efficacy of treatment was determined by the decrease in abscess bacterial counts and abscess weights, as well as by the reduction in inflammation (biodistribution of (99m)Tc-HYNIC immunoglobulin G) compared to saline-treated controls. Trovafloxacin showed a significant dose-response effect on the bacterial counts, weight, and inflammation of B. fragilis-E. coli abscesses after 3 and/or 5 days of treatment. A maximum 3.4 and 3.1 log(10) reduction in CFU/abscess in the respective B. fragilis and E. coli bacterial counts was attained after 5 days of treatment with daily doses of 300 mg/kg. The peak serum concentration was more predictive for effect than the area under the concentration-time curve. The C(max) was the pharmacodynamic index most predictive for success, and the efficacy of the q24h regimens was significantly better than the q8h regimens. The antibiotic was ineffective against the VREF in mixed infection with B. fragilis, while the killing of the anaerobe in the same combination was significantly less than in the E. coli combination (P < 0.05). We conclude that this is a useful model for studying the activity of antimicrobials for the treatment of small (<1-cm), undrainable, mixed-infection abscesses. In addition, we have shown for the first time that a decrease in bacterial numbers also leads to a reduction in both abscess weight and inflammation.
Abscess↗
Nuclear medicine techniques for the diagnosis and therapy of prostate carcinoma.
Nuclear medicine techniques play an important role in (re)staging and treatment of prostate carcinoma patients. These techniques are reviewed in this paper. For many years, bone scanning has been a valuable tool for the evaluation of bone metastases. Although utilized in a more refined way since the introduction of serum prostate-specific antigen (PSA) measurement, it is still the procedure of choice in patients with higher-grade or higher-stage tumors and elevated or rising PSA levels. Labeled monoclonal antibodies have been found to have some utility in the clinic for the evaluation of disseminated malignant prostate disease and position emission tomography holds promise for the metabolic characterization of prostate cancer. Several agents are available for radionuclide therapy for bone pain palliation in patients with metastasis, improving pain with minimal side effects or discomfort to the patient. Nuclear medicine techniques in prostate carcinoma are far from obsolete. On the contrary, they are evolving and offer unique opportunities for the management of these patients. The bone scan remains useful in well-defined stages of disease, and palliative therapeutic options are evolving. At present, monoclonal antibodies and PET are not very useful in daily clinical practice.
Antibodies, Monoclonal↗