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Biomedical subjects

G J Teule

Publications and source records attributed to G J Teule.

At least 55 records · Page 3Linked to original sources
PubMed1995

Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Feasibility of planar fluorine-18-FDG imaging after recent myocardial infarction to assess myocardial viability.

UNLABELLED: The aim of this study was to define the clinical feasibility of planar myocardial 18F-fluorodeoxyglucose (FDG) imaging and to assess the relation between 201Tl, FDG and left ventricular function early after myocardial infarction. METHODS: Fifty-one patients were studied 5 +/- 2 days after infarction. Scintigraphic images were visually and quantitatively analyzed using a circumferential profiles technique. FDG uptake was normalized to the area with maximal 201Tl uptake. Scintigraphic data were compared with left ventricular wall motion as assessed by ventriculography in 22 patients. Relative regional 201Tl uptake was categorized as normal (> or = 75% of peak activity), moderately reduced (50%-75%) or severely reduced (< 50%). These tracer defects were considered viable if FDG uptake exceeded 201Tl uptake by > or = 20% and/or if FDG uptake was normal (> or = 75%). All regions with FDG uptake 20% less than 201Tl uptake were considered nonviable. RESULTS: Four hundred forty-one myocardial regions were analyzed; 200 showed normal 201Tl uptake, 241 had reduced uptake, 191 had moderately reduced 201Tl uptake and 50 regions had severely reduced uptake. Viability for moderately and severely reduced regions was observed in 62% and 48%, respectively. A concordance between flow and metabolism was observed in 38% and 52%, respectively. CONCLUSION: Myocardial FDG imaging is feasible with standard gamma camera systems and enables the identification of regions with preserved glucose metabolism in patients shortly after infarction.

Coronary Angiography↗
PubMed1994

A dosimetric model for intrathecal treatment with 131I and 67Ga.

PURPOSE: Calculations were performed of absorbed dose distributions of the beta-emitter 131I and the Auger emitter 67Ga for intrathecal administration. METHODS AND MATERIALS: The proposed dosimetric model accounts for the macroscopic distribution of the activity, by means of a Medical Internal Radiation Dose Committee approach, and for the microscopic distribution of activity, by means of a point kernel technique. This point kernel approach was used in combination with a distance histogram technique, to study in more detail the absorbed dose distribution in the cerebro-spinal fluid, in the surface of the central nervous system, and in tumor sites. We simulated decreased uptake, as well as highly selective uptake in free-floating tumor cells and in meningeal lesions (1-16 cells thick). RESULTS: In case of limited access to lesions adherent to the pia mater, the beta-emitter 131I provides crossfire from the CSF, resulting in a higher absorbed dose (Gy/MBq) in these lesions as compared with the Auger emitter 67Ga. In case of increasing radionuclide uptake, the increment of the absorbed dose in the adherent lesions and the free floating cells from 67Ga is considerable because of the local deposition of energy by this radionuclide. CONCLUSIONS: The model might be useful to select the optimal emission characteristics of radionuclides applicable for intrathecal therapy, which is demonstrated in a comparison of the Auger emitter 67Ga and the beta-emitter 131I.

Gallium Radioisotopes↗
PubMed1994

Biological effectiveness of 67-gallium decay in HL60 cells compared with external low dose rate gamma irradiation: effects on proliferation, G2 arrest, and clonogenic capacity.

PURPOSE: Estimation of the relative biological effectiveness of electron emissions of 67Gallium for cell growth delay and inactivation. METHODS AND MATERIALS: Human myeloid HL60 cells were incubated in vitro with 0.74 MBq/mL, 1.48 MBq/mL, or 2.96 MBq/mL of 67Gallium for 4 days. Proliferation (vital cell counts and colorimetric tetrazolium assay), clonogenic survival, and cell-cycle effects were compared with responses of HL60 cells externally irradiated with 0.78, 10.37, and 13.22 Gy by an external 67Gallium source. Dosimetric calculations were performed by Monte Carlo simulations (10,000 events). RESULTS: Proliferation of cells was equally inhibited after 67Gallium incubation with 1.48 and 2.96 MBq/mL compared with 10.37 and 13.22 Gy external irradiation. Irradiation with 10.37 and 13.22 Gy caused a 81% and 89% reduction of Colony Forming Units, compared with 34%, 66%, and 80% reduction after 67Gallium incubation with 0.74, 1.48, and 2.96 MBq/mL, respectively. Peak values for G2/M accumulation were reached on day 4 for the cells externally irradiated with 10.37 and 13.22 Gy (47.5% and 56.7%) and on day 5 after 67Gallium incubation with 0.74 MBq/mL, 1.48 MBq/mL, and 2.96 MBq/mL (26.7%, 43.4%, and 58.2%). CONCLUSIONS: 67Gallium incubation exerts a significant cytotoxic effect on human HL60 cells, which, on the basis of dosimetric studies, may be mainly ascribed to conversion electrons (80 KeV) and 8 KeV Auger electrons. Low energy (< 1 keV) Auger electrons do not contribute significantly. The relative biological effectiveness of 67Gallium compared with external low dose rate gamma irradiation is about 1.0 for clonogenic survival and approximately 1.8 and 1.5 for proliferation inhibition and G2 arrest, respectively. For in vivo therapy, this might implicate that higher doses of 67Gallium than 131Iodine or 90Yttrium are necessary for the same biological effect.

Cell Count↗
PubMed1994

Weight-bearing activity during youth is a more important factor for peak bone mass than calcium intake.

In a 15 year longitudinal study (Amsterdam Growth and Health Study) is evaluated the effect of daily calcium intake (CAI) during adolescence and young adulthood on the development of peak bone mass at age 27 when the influence of weight-bearing activity (WBA) and body weight was accounted for. A group of 84 males and 98 females were measured longitudinally from age 13 until age 28. Measurements were taken six times of anthropometric characteristics. Lifestyle was also evaluated six times by cross-check interviews of CAI and WBA. Bone mineral density (BMD) of the lumbar spine was determined at age 27 by dual x-ray absorption. Three periods were considered, that is, the adolescent period, the period 13-21 years, and the total period (13-27 years). In multiple linear regression analyses, only WBA and body weight were significant positive contributors to the final model of lumbar BMD at age 27. In all three periods WBA was the best predictor in males and body weight in females. ANOVA was performed on BMD and the highest and lowest quartiles of calcium intake with the significant predictor variables of the linear regression model as covariates. Again calcium intake appeared not a significant predictor of BMD in the three periods in both sexes. Regular weight-bearing exercise and at least a normal age-related body weight in adolescence and young adulthood are of key importance in reaching the highest lumbar peak bone mass at the age of 27 years.

Absorptiometry, Photon↗
PubMed1994

Consequences of childhood-onset growth hormone deficiency for adult bone mass.

To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies.

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium-111-OV-TL-3 F(ab')2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111In-OV-TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16.88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.

Bone Marrow↗
PubMed1994

Intra-arterial infusion of Tc-99m MAA: a case of highly selective targeting of liver metastases and shunting.

A patient with liver metastases and on angiotensin-converting enzyme inhibition for hypertension was studied after administration of Tc-99m MAA through the hepatic artery. The scintigrams showed a highly selective perfusion of the metastases (and significant shunting) despite the systemic treatment with a vasoactive drug that, theoretically, diminishes the flow to metastases. A possible effect of concomitant vasoactive medication on targeting and systemic side effects should be considered if regional perfusion studies and intra-arterial treatment are performed.

Enalapril↗
PubMed1994

Delayed resolution of pulmonary oedema after cocaine/heroin abuse.

Pulmonary oedema lasting six days occurred in a 68 year old man after sniffing cocaine. He also had evidence of parenteral self-administration of heroin. Pulmonary microvascular filtration pressure and permeability were normal. Delayed resolution of the pulmonary oedema may have been caused by a cocaine-induced impairment of sodium and thus fluid transport across alveolar epithelium. Recognition may be important, since lowering filtration pressure with diuretics may not hasten resolution of oedema.

Aged↗
PubMed1994

Loss of bone in the proximal part of the femur following unstable fractures of the leg.

We evaluated the subsequent loss of bone from the proximal part of the ipsilateral and contralateral femora and from the lumbar spine of seven men and nine women who had a fracture of the tibia. The average age was sixty years. All of the fractures were unstable, and the involved leg bore no weight for an average of eight weeks. The bone mineral density was measured with dual-energy x-ray absorptiometry of the lumbar spine and of the femoral neck and the trochanteric region of both hips immediately after the fracture, after the period of immobilization, and at approximately three, six, and twelve months after the fracture. During the period of immobilization, the bone mineral density of the trochanteric region decreased an average of 9 +/- 7 per cent on the side of the fracture, compared with the value immediately after the fracture, but there was no change on the contralateral side (p < 0.01). At twelve months, the average decrease in the trochanteric area was 15 +/- 10 per cent on the side of the fracture, compared with the value immediately after the fracture, but again there had been no change on the uninjured side (p < 0.01). The bone mineral density of the femoral neck on the side of the fracture had decreased 6 +/- 6 per cent at twelve months, compared with a decrease of 2 +/- 4 per cent on the uninjured side (p < 0.05). The bone mineral density of the lumbar spine decreased only during the period of unloading of the fractured leg (1 +/- 2 per cent, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

Early response monitoring in malignant lymphoma using fluorine-18 fluorodeoxyglucose single-photon emission tomography.

Metabolic response monitoring early during chemotherapy may have a major impact on clinical management of patients with malignant lymphoma. In two patients with non-Hodgkin's lymphoma fluorine-18 fluorodeoxyglucose (18FDG) single-photon emission tomography (SPET) studies were performed during the first two chemotherapeutic cycles. Persisting uptake predicted treatment failure whereas a sharp reduction of 18FDG uptake was demonstrated in the case of a responsive tumour. Qualitative analysis of conventional 18FDG imaging may thus serve to identify patients with a non-responding tumour. The potential of this technique in the determination of the initial response remains to be established. Imaging with 18FDG and SPET appears promising as a more easily available methodology than 18FDG positron emission tomography.

Adult↗
PubMed1993

Hypophyseal non-Hodgkin's lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy.

A patient is described with a testicular Non-Hodgkin's Lymphoma (NHL) presenting with panhypopituitarism caused by a hypophyseal localization. A 67Gallium scintigraphy showed avid uptake in the hypophyseal region. Obviously 67Gallium could reach the tumor, by the intravenous route, which was the reason to treat the patient with intravenous chemotherapy. A complete remission was induced, which seems to be lasting (+25 months). As far as we know this is the first report of panhypopituitarism caused by a hypophyseal NHL in the hypophysis and successfully treated by intravenous chemotherapy.

Aged↗
PubMed1993

Gallium-67 radiotoxicity in human U937 lymphoma cells.

Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use.

Cell Division↗
PubMed1993

Gallium 67 in the human lymphoid cell line U-715: uptake, cytotoxicity and intracellular localization.

The selective uptake of the Auger- and internal conversion electrons emitting radionuclide 67Ga in malignant tumours may have therapeutic potential. We studied several factors which might affect the uptake and radiotoxicity of 67Ga in the human lymphoma cell line U-715. The 67Ga uptake was dependent on transferrin in a dose-dependent manner. The highest 67Ga uptake was found in the presence of 50 micrograms/ml purified human transferrin. Serum components other than transferrin negatively influenced the 67Ga uptake. Cells were adapted to a serum-free medium in which cells could be maintained for months and without factors disturbing 67Ga uptake. We demonstrated that there was a positive correlation between cell viability and 67Ga uptake (r = 0.97). Preculturing of cells in iron- and transferrin-deficient medium prior to 67Ga uptake led to upregulation of the transferrin receptor and a three-fold increase of 67Ga uptake. Uptake in these cells could be blocked by 72% by anti-transferrin-receptor monoclonal antibodies. Autoradiography of U-715 cells after 67Ga incubation showed intracellular 67Ga both in the cytoplasm and nucleus. Cell fractionation of 67Ga-loaded cells showed 27% of 67Ga present in the nuclei. Culturing of cells for 4 days in the presence of 3 MBq/ml 67Ga resulted in a 45% decrease of cell proliferation. The clonogenic capacity was diminished by 91%. In conclusion, we have demonstrated that 67Ga uptake is a transferrin-receptor-dependent mechanism of vital cells, and that after uptake 67Ga enters the cytosol and nucleus and has a strong cytotoxic effect on clonogenic capacity.

Cell Line↗
PubMed1993

Feasibility of assessing regional myocardial uptake of 18F-fluorodeoxyglucose using single photon emission computed tomography.

Differentiation between viable myocardium and scar tissue in segments with abnormal contraction has important consequences in the clinical management of patients with coronary artery disease. Positron emission tomography (PET) can identify viable tissue using 18F-fluorodeoxyglucose (FDG). However, application of PET for daily routine is limited. In this study, FDG uptake was visualized with single photon emission computed tomography (SPECT) and compared with regional perfusion assessed with thallium-201 (201Tl) SPECT. The scintigraphic findings were related to regional wall motion determined with two-dimensional echocardiography. Patients (n = 9) with wall motion abnormalities underwent FDG SPECT and resting 201Tl SPECT. To control the metabolic status patients were studied with a hyperinsulinaemic euglycemic clamp during FDG SPECT. Analysis of reconstructed data was performed visually and semiquantitatively using circumferential profiles. High-quality images were obtained. Eight 201Tl defects showed concordantly decreased FDG uptake (metabolism-perfusion matches) indicating scarred tissue, whereas six regions of hypoperfusion demonstrated a relatively increased FDG uptake (mismatches), suggesting viable myocardium. Semiquantitative analysis confirmed visual findings. Mean 201Tl and FDG activities were not significantly different in matching defects. In mismatches the mean FDG activity was 81 +/- 11% vs 64 +/- 9% mean 201Tl activity (P < 0.0001). In four of six segments with increased FDG uptake, two-dimensional echo revealed hypokinesia. Seven of eight regions with a matching defect in contrast were akinetic. Thus, in the areas with a mismatch contractility was preserved. We conclude that FDG uptake can be visualized with SPECT. Furthermore, our preliminary observations suggest that this approach can identify viable tissue.

Adult↗
PubMed1993

Therapeutic potential of intravenous 67-gallium in non-Hodgkin's lymphoma.

67-gallium accumulates rather selectively in malignant lymphoid tissue. The isotope has a substantial cytotoxic effect in human-derived cell-lines. 67-gallium was given intravenously to 3 patients with end-stage, resistant large-cell lymphoma. Evaluation of tumour response was done by physical measurements, and CT-scanning together with gallium scintigraphy. Three weekly doses of 20, 40 and 60 mCi respectively caused persistent pancytopenia in 1 patient. Pancytopenia was not observed in 2 other patients given two 40 mCi doses 4 weeks apart. In all 3 patients, some response was noted, be it shortlived and different from site to site. 67-gallium has some cytostatic effect in large cell lymphoma. It seems feasible to start a phase I study to find a tolerable dose to be given every 4 weeks.

Adult↗
PubMed1993

Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery.

STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial study. SETTING: Department of nuclear medicine and intensive care units of a university hospital. PATIENTS: Twelve consecutive patients were studied, before and immediately after elective cardiac surgery using CPB (group 1), and 4 consecutive, artificially ventilated patients with acute cardiogenic pulmonary edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both lungs were measured, using two mobile probes at the bedside, of intravenously injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc-labeled red blood cells to account for pulmonary blood volume. From data recorded in time (1 h), a pulmonary leak index (PLI), the time constant of transport of 67Ga from the intravascular to the extravascular space of the lung, was calculated and values for both lungs were averaged. In group 1, the PLI (.10(-3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery (p < 0.01) and changes directly related to the duration of CPB. In four patients with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded 2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to changes in arterial WBC, which, in turn, inversely related to CPB duration. The PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No patient developed alveolar pulmonary edema on chest radiograph. In group 2, the PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI). CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as assessed by 67Ga kinetics using a bedside detection technique, in some cardiac surgery patients with prolonged CPB. This leak may reflect pulmonary vascular injury and increased permeability, following activation of leukocytes by CPB and subsequent pulmonary sequestration, rather than increased filtration through pressure factors. It may contribute to impaired gas exchange, even in the absence of manifest alveolar edema of the lungs, after surgery.

Acute Disease↗