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Biomedical subjects

J A Camps

Publications and source records attributed to J A Camps.

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

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

No effect of misoprostol on renal function of rheumatoid patients treated with diclofenac.

Non-steroidal anti-inflammatory drugs can reversibly decrease renal function in patients with rheumatoid arthritis (RA). To test whether orally administered prostaglandins could mitigate this decrease, we studied the effect of misoprostol in 24 RA patients during treatment with diclofenac in a randomized, placebo-controlled crossover trial. At baseline, 21 patients had a creatinine clearance below 80 ml/min/1.73 m2. The two treatment phases (with either misoprostol, 600 micrograms daily, or matching placebo tablets) were separated by a washout phase in which diclofenac (150 mg daily) was continued. After treatment with misoprostol/diclofenac the glomerular filtration rate was 72 +/- 5 ml/min (mean +/- standard error), and the effective renal plasma flow was 295 +/- 21 ml/min. After treatment with placebo/diclofenac, the corresponding values were 71 +/- 5 ml/min and 296 +/- 21 ml/min, respectively. We concluded that misoprostol has no effect on the renal function of RA patients treated with diclofenac.

Adult

Right ventricle wall motion abnormalities in patients treated with chemotherapy.

Doxorubicin is a cytotoxic agent used in the treatment of patients with various malignancies. Its clinical value is limited by a dose-related cardiotoxicity. Wall motion was analyzed in 52 patients during different stages of treatment. Eleven patients were studied once, and in 41 patients serial radionuclide ventriculography was performed from 2 to 5 times. Abnormal wall motion was found in 96 out of 1,062 segments (9.0%), of which 33 out of 735 (4.5%) were in the left ventricle (LV) and 65 out of 327 (19.9%) were in the right ventricle (RV). The number of abnormalities in the RV was significantly higher than in the LV (P less than 0.001). Regional analysis of LV and RV in 109 40 degrees LAO studies and in 102 75 degrees LAO studies showed abnormal wall motion in the following segments: LV--posterobasal 6 (5.9%), inferior 2 (2.0%), anterior 5 (4.9%), anteroseptal 11 (10.1%), apical 5 (4.6%), posterolateral 4 (3.7%); RV--septal 44 (40.4%), apex 15 (13.8%), and the free wall 6 (5.5%). The left ventricular ejection fraction decreased from 74% median (M) in baseline studies to 54% (M) in the highest dose group (greater than 650 mg/m2). The present data show an increased number of wall motion abnormalities in the RV compared with the LV, particularly in the RV septum (P less than 0.001).

Antineoplastic Combined Chemotherapy Protocols

Detection of a local staphylococcal infection in mice with technetium-99m-labeled polyclonal human immunoglobulin.

The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02).

Animals

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

Subclinical renal dysfunction in rheumatoid arthritis.

We studied renal function in 35 patients with chronic, seropositive rheumatoid arthritis (RA), of whom 7 had vasculitis, 10 had hypergammaglobulinemia, and 18 had neither of these 2 conditions. Findings included a decreased glomerular filtration rate in 8 patients, (micro)proteinuria in 11, a defective urine concentration in 10, and increased urinary tubular enzyme levels in 15. These results indicate that subclinical renal dysfunction is common in patients with chronic, seropositive RA. In addition, vasculitis and hypergammaglobulinemia were not identified as risk factors for renal dysfunction in the RA patients studied.

Arthritis, Rheumatoid

Abnormal septal motion after aortic valve replacement for chronic aortic regurgitation: no evidence for myocardial ischaemia by exercise radionuclide angiography.

To evaluate interventricular septal motion and left ventricular function after aortic valve replacement for chronic aortic regurgitation, we studied 12 patients at rest and during exercise by radionuclide angiography after a mean of 19 (range 12-36) months after operation (group I). Twenty patients with chronic aortic regurgitation without aortic valve replacement served as controls (group II). None of the patients had coronary artery disease as documented by arteriography. Abnormal interventricular septal motion at rest was seen in 11 patients of group I, of whom 8 showed hypokinesis and 3 akinesis. During exercise, the interventricular septal wall motion improved in 4 patients, worsened in 3 patients and did not change in 5 patients. All patients of group II had normal interventricular septal motion at rest. During exercise, 5 patients showed septal wall hypokinesia together with apical and posterolateral wall motion abnormalities. The left ventricular ejection fraction at rest was 62% +/- 20% in group I and 66% +/- 8% in group II (not significant). During exercise, the left ventricular ejection fraction was 59% +/- 24% in group I and 68% +/- 13% in group II (not significant). We conclude that abnormal interventricular septal motion at rest is commonly found in patients with aortic valve replacement for chronic aortic regurgitation. During exercise, septal wall motion in the patients with aortic valve replacement shows a variable response from complete normalization to akinesia. These findings are mostly associated with a normal global left ventricular function both at rest and during exercise, which precludes myocardial ischaemia as a primary cause for abnormal septal wall motion after aortic valve replacement.

Adult

Detection of inflammatory lesions with radiolabelled immunoglobulins.

Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials of Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection were injected with Tc 99m-immunoglobulin, Tc 99m-albumin or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with gallium.

Animals

Comparison of four commercially available 81Rb-81mKr generators: quality testing using a breathing lung phantom.

Four commercially available 81Rb-81mKr generators, including their elution systems, were compared. Considerable differences in useful output between the various generators were found. When a standardized elution system was used, the differences became much less. Differences in the tubing and inaccuracy of the flow meters were found to be the major causes of the original differences. The user should be aware of a loss of output that may occur when the generator is eluted with dry air.

Humans

Imaging of acute myocardial infarction in pigs with Indium-111 monoclonal antimyosin scintigraphy and MRI.

Indium-111 antimyosin F(ab')2 was used in a series of scintigraphic studies on experimentally induced myocardial infarctions in pigs. Antimyosin distribution recorded by planar images of in vivo pigs and by single photon emission computed tomography (SPECT) of excised hearts delineated areas of myocardial necrosis if infarct volume exceeded 3.3 cm3. Scintigraphic images were compared with magnetic resonance images (MRI) obtained from excised hearts and with photographs of slices of the hearts. Infarct size and localization determined with antimyosin were compared. The MR images, with or without gadolinium-DTPA (Gd-DTPA), of the in vivo pigs were all false-negative; some myocardial wall thinning and high bloodpool signals were visible. Results show that both the antimyosin and the MR technique are specific methods for the visualization of induced myocardial necrosis in this animal model. However, the use of antimyosin is limited to a period ranging from 24 to 72 hours after infarction.

Animals

Lymphoscintigraphy and lymphedema of the lower extremities.

Lymphoscintigraphy, using technetium-99m-labeled sulphur microcolloid, was employed to study the flow and transport of lymph in the lower extremities of 39 consecutive patients in whom lymphedema of one or both legs was suspected clinically. Time-activity curves of four segments of each leg were evaluated for lymph capacity, flow and soft-tissue uptake, and compared with the results from film scintigraphy. Curve analysis provided quantitative evaluation of the extent of hypoplasia or aplasia in primary lymphedema and of lymphatic obstruction in secondary lymphedema, and is particularly suited to assess the involvement of lymphatics in chronic venous disease. Film scintigraphy, on the other hand, is preferable in cases in which the pattern of activity distribution in the affected extremity is diagnostic, such as in dermal back flow, traumatic lymphocele, or megalymphatics. Venography is most informative in cases of suspected underlying venous disease, but the role of lymphangiography, which shows only part of the lymphatic system and requires incision of the edematous tissues, is considered questionable.

Adult

Precision of dual photon absorptiometry measurements: comparison of three different methods of selection of the region of interest.

To determine the short-term reproducibility of bone mass calculations with dual photon absorptiometry of the lumbar spine (L2-L4), duplicate measurements in healthy subjects were used. Three different methods for selection of region of interest were compared: a rectangular region with variable height and width, an irregular region to be drawn freely by the operator and the standard calculation software supplied with the bone densitometer. Contributions of changes in size and location of the region of interest on calculated bone mineral mass were also investigated. An increase in height of the region by 2 scan lines caused an increase in bone mineral content (BMC) of 8.4% +/- 1.8%. Enlargement in width by 2 pixels in each scan line caused an increase in BMC of 2.5% +/- 1.3%. The difference between these region of interest changes was significant (P less than 0.0005). The use of a rectangular region, optimized to enclose L2-L4 in each person but of the same size in both measurements, resulted in a reproducibility of 1.4% and 0.7% respectively for 2 observers, with an inter observer variation of 1.2%. The reproducibility of the duplicate measurements was worse for the other methods of region of interest selection. A further series of duplicate DPA measurements in normal subjects, but with a standard meal between the measurements, showed a larger variation in the results. Again the reproducibility of the calculations using the rectangular region was better than with the other methods, with much less inter observer variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Radioimmunoscintigraphy with melanoma-associated monoclonal antibody fragments in choroidal melanoma.

A prospective pilot study on radioimmunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was carried out in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma-associated antigen were labeled with 740 mBq 99mTc and injected IV; images were made with a gamma camera at 6 h after injection. With a double-pinhole collimator, radioactivity was counted thrice in both eyes at 6 h after injection. In 6 of 16 patients (37.5%), the melanoma could be imaged with the gamma camera. With the double-pinhole collimator, a significantly higher activity was measured in the melanomatous eye in 13 of 16 patients (82.4%). In two patients a false negative result was obtained, and in one patient the difference between the left and right eye was not significant. Considering these results, radioimmunoscintigraphy may be valuable in ocular melanoma diagnostics, but the specificity of MoAb 225.28S needs to be assessed.

Adult

An in vitro model for the scintigraphic detection of thrombi using a 99Tcm-labelled antifibrin monoclonal antibody.

Because of their specific targeting properties, monoclonal antibodies have found widespread use in nuclear medicine. In this paper, a method is described for the evaluation of immunoscintigraphic parameters for the detection of thrombi, using a 99Tcm-labelled antifibrin monoclonal antibody (designated as Y22). An in vitro model was developed to evaluate the effects of various environmental conditions on uptake by plasma clots of 99Tcm-Tc-Y22 in circulating plasma on a gamma camera. The clots became visible as hotspots after approximately 1 h of circulation of 99Tcm-Y22 containing citrated plasma at 37 degrees C. Circulation of 99Tcm-fibrinogen, 99Tcm-HSA or 99Tcm-control MoAb did not show visible uptake by the clots under the same conditions. At 37 degrees C, 99Tcm-Y22 accumulated approximately four times faster than at 20 degrees C. Heparin did not affect binding of the antibody to clots. To assess the feasibility of thrombus detection in vivo, an extracorporeal rat thrombus model was used. A thrombus in a shunt between a carotid artery and a jugular vein became visible 1 h after injection of the labelled Y22 and, more clearly, after 3 h.

Animals

Imaging of inflammatory arthritis with technetium-99m-labeled IgG.

The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of [99mTc]albumin and [99mTc]nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with [99mTc]IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

Animals

Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.

To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.

Adult