Long-term consequences of 239PuO2 exposure in dogs: persistent T lymphocyte dysfunction.

Young Beagle dogs were exposed by inhalation to aerosols of 239PuO2 and observed for their lifespans as part of a large, ongoing study of the biological effects of inhaled radionuclides. The purpose of our study was to compare certain immune responses of the 239PuO2-exposed dogs at middle age (7-10 years old) and old age (12-14 years old), with those of unexposed, age-matched or young (3-4 years old) animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte proliferative responses to phytohaemagglutinin (PHA) were lower in aged control dogs than in either young or middle-aged control dogs. Both aged and middle-aged, radiation-exposed dogs had decreased responses to PHA when compared to age-matched controls. Responses to concanavalin A (Con A) were not affected by age in control dogs, but tended to decrease in the oldest group of radiation-exposed dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing dogs. The cytolytic activity of natural killer cells was not affected by age, radiation exposure, or tumour presence. We concluded that inhalation of 239PuO2 by young Beagle dogs resulted in an earlier-than-normal decrease in the ability of T cells to respond to mitogenic stimulation. In other words the depressed responses to PHA that were observed might represent radiation-induced, accelerated ageing of the T cell response.     

Translocation of Plutonium from Rat and Monkey Lung after Inhalation of Industrial Plutonium Oxide and Mixed Uranium and Plutonium Oxide

This study was designed to compare the translocation from lung of the Pu contained in the pure and mixed industrial oxides PuO₂ and (U,Pu)O₂. The latter had a Pu content of 20% w/w. For this purpose, young adult male rats and male and female baboons were exposed to a single inhalation of these oxides. Two baboons were exposed to the reference PuO₂, i.e. ²³⁹PuO₂. Rats were killed under anaesthesia 1, 15, 30, 90 and 180 days after exposure, and baboons, also under anaesthesia, 1 year thereafter. The results indicate that lung retention of Pu was independent of the oxide inhaled, but was smaller in rat (12–15% of the initial pulmonary burden, 6 months after exposure) than in baboon (56–80% of this burden, 1 year after exposure). In rat, Pu translocation kinetics were similar for the two industrial oxides, but as from day 15 after inhalation until 6 months thereafter, measurement of Pu deposits in the liver and skeleton showed that translocation of Pu from the mixed oxide was 2–3 times greater than that from the industrial Pu oxide. In baboon, the largest amounts of Pu were retained in the lung and thoracic lymph nodes for the three oxides inhaled. Pu translocation to the liver, skeleton and kidneys, and also urinary Pu excretion, were greater after inhalation of the mixed oxide than after inhalation of the industrial and reference Pu oxides. Nevertheless, the amount of mixed oxide Pu translocated to these sites and excreted in urine remained under 3% of the initial pulmonary burden.     

Long-term Changes in Mouse Lung Following Inhalation of a Fibrosis-inducing Dose of 239PuO2: Changes in Collagen Synthesis and Degradation Rates

Summary

Mice were exposed by nose-only inhalation to ²³⁹PuO₂, which resulted in an IAD of 1110 ± 29 Bq. At various times after exposure, rates of collagen metabolism were measured using validated in vivo methods based on the administration of radiolabelled proline, together with a large flooding dose of unlabelled proline and measurement of its incorporation into lung collagen as hydroxyproline. Dramatic increases in both synthesis and degradation rates of collagen were observed. At 54 days after exposure the fractional synthesis rates in experimental mice were almost five times those in controls (control: 3·2 ± 0·6%/day, ²³⁹PuO₂-exposed: 14·5 ± 0·4%/day) and by 300 days synthesis rates, although declining, were still more than double the control values. A similar pattern of change was observed for collagen degradation. The combination of changes in synthesis and degradation rates led to a 60% increase in lung collagen content by 300 days (control: 3·05 ± 0·24 mg/lung, ²³⁹PuO₂-exposed: 4·88 ± 0·42 mg/lung). The data suggest that extensive remodelling of the lung connective tissue matrix occurs during development of fibrosis and that, over long periods of time, small imbalances between synthesis and degradation may result in quite large increases in protein content.     

Preliminary Studies of the Interaction between 239PuO2 and Cigarette Smoke in the Mouse Lung

Summary

Our current experiments were designed to show whether 12 months' exposure to cigarette smoke enhances the incidence of lung tumours in mice that had previously inhaled ²³⁹PuO₂. These periods of smoke exposure are almost complete. After death their lungs will be cleared and any nodules found will be sectioned for histopathology. This paper reports the results of two preliminary experiments conducted earlier.

The first study showed that mice could tolerate the proposed smoking regime for 3 months, with no sign of ill health in any animal throughout. The major difference found was a reduced growth rate in both smoke- and sham-exposed mice relative to that of cage controls. After 3 months of treatment, histopathology and morphometry of lung sections found only slight smoke-induced changes. These included a reduced proportion of alveolar space and an increased number of pulmonary alveolar macrophages (PAM) per unit area. Bronchopulmonary lavage showed that the PAM from smoke-exposed mice were larger than those from sham-exposed or control mice and that an increased proportion of cells were binucleate.

All mice in the second study were initially exposed to ²³⁹PuO₂, then subsequently divided into three treatment groups as above. Cigarette smoke exposure was shown to inhibit the removal of ²³⁹Pu from the lung whilst sham exposure had no effect. Smoke exposure also produced an increase and sham exposure a decrease in lung weights relative to those of cage controls. The latter was probably as a result of their lower growth rate. In our current experiments it is likely that the group receiving ²³⁹PuO₂, then smoke, will receive a higher radiation dose to lung than those receiving ²³⁹PuO₂ only. Any increased tumour incidence found will be considered in conjunction with this evidence.     

Pulmonary immune response of dogs after exposure to 239PuO2

This study evaluated the cell-mediated (CMI) and humoral immune responses in four Beagle dogs five to six years after single inhalation exposures to different monodisperse 239PuO2 aerosols (0.72-1.4 microns activity median aerodynamic diameter). These exposures resulted in initial lung burdens ranging from 19 to 35 kBq. Four nonexposed dogs were used as age-matched controls. Anesthetized dogs were immunized by instillation of sheep red blood cells (SRBC) into selected lung lobes. Cells and fluids were obtained serially from blood samples and by bronchoalveolar lavage of the saline- and SRBC-treated lung lobes at 5-20 days after immunization. The CMI response evaluated by the leukocyte procoagulant activity test was similar in the saline- and SRBC-treated lobes of both groups of dogs. The humoral immune response was measured by the enzyme-linked immunosorbent assay. No differences were shown between the amount of antibody measured in the sera or lung lavages from control or Pu-exposed dogs. Histopathology of the tracheobronchial lymph nodes from the Pu-exposed dogs showed them to be fibrotic with no lymphoid cells, suggesting that these tissues could not respond to the antigen deposited in the lungs. However, both mediastinal and sternal lymph nodes did contain lymphoid tissue, and were likely to be the lymphoid tissues that produced the immunity to the antigen deposited in the lungs of the exposed dogs. Although both exposed and control dogs produced immune responses to the antigen instilled into their lungs, differences were observed in the number of neutrophils in lung lavages from the control and exposed animals. There was a dramatic influx of neutrophils into both the saline- and SRBC-treated lung lobes of the Pu-exposed dogs that was not seen in the age-matched controls. This suggests that the inhaled 239PuO2 produced chronically-active inflammation in the lung which may contribute to recruitment of lymphocytes to the lung following intrapulmonary deposition of antigen. In conclusion, the immune responses induced by lung immunization of dogs that had inhaled 239PuO2 were not suppressed by large doses of chronic alpha irradiation of the lungs and tracheobronchial lymph nodes, indicating that local pulmonary immune responses are preserved despite severe radiation-induced alteration of these tissues.     

The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer

Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (⁹⁰Sr), cerium-144 (¹⁴⁴Ce), yttrium-91 (⁹¹Y), or yttrium-90 (⁹⁰Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed.

Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DR_ef).

Results: Dogs exposed to DRef (1–100?Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10?Gy/day) died of lung cancer. As DR_ef decreased further (<0.1?Gy/day ⁹⁰Sr, <0.5?Gy/day ¹⁴⁴Ce, <0.9?Gy/day ⁹¹Y, <8?Gy/day ⁹⁰Y), survival and lung cancer frequency were not significantly different from control dogs.

Conclusion: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.     

Standardisation of tracer and type of meal in the evaluation of gastric emptying and colon transit rates in normal Beagle dogs

The transit of ¹¹¹In-labelled polymer beads of different particle sizes in the stomach and colon of five healthy Beagle dogs was monitored after intake of different kinds of meal by a gamma camera and data processor system. The various meals studied were a solid balanced type of dog food mixed with milk, pure milk, and finally a meal of raw meat. The polymer beads carried triethylenetetramine type functions which efficiently chelated ¹¹¹In⁺³ from an aqueous solution of InCl₃. These labelled beads were well mixed into the food before being offered to the dogs. Gastric emptying curves from which half-times of emptying (T_1/2) could be obtained are presented and statistically compared. Good quality images with quantification of the colon transit rate also became possible. It appeared that standardisation of the tracer and of the meal is compulsory for relevant and reproducible results.     

Effects of age-related changes in step length and step width on the required coefficient of friction during straight walking

BackgroundSlipping is one of the leading causes of falls among older adults. Older adults are considered to walk with a small anteroposterior (AP) component and a large mediolateral (ML) component of the required coefficient of friction (RCOF) owing to a short step length and a wide step width, respectively. However, limited information is available.Research questionWhat are the effects of aging on the resultant RCOF (RCOF_res) and its ML (RCOF_ML) and AP (RCOF_AP) components during straight walking?MethodsWe used the kinetic and kinematic data of 188 participants aged 20–77 years from a publicly available database (National Institute of Advanced Industrial Science and Technology Gait Database 2015). The participants were divided into the following three groups: young group (n = 56; age range, 20–34 years), middle-aged group (n = 50; age range, 35–64 years), and old group (n = 82; age range, 65–77 years).ResultsThe RCOF_res and RCOF_AP were lower in the old group than in the other groups, indicating a lower slip risk in this group. However, the RCOF_ML was higher and the step width was greater in the old group than in the other groups. The higher RCOF_ML and lower RCOF_AP in the old group might be associated with slips in a more lateral direction.SignificanceOur findings suggest that older adults have a high risk of slipping in a more lateral direction. Shoes with high-slip resistance in the lateral direction are recommended to prevent hazardous lateral slips among older adults.     

大鼠吸入239PuO2后的肺癌剂量效应关系

306只吸入²³⁰PuO₂气溶畦大鼠中,肺癌发生宰(Y,%)与肺累积平均吸收剂量(D,Gy)关系,符合于拟台方程Y=105exp[-3.57/(D+1.25)],由此方程推算出大鼠吸入。抽²³⁰PuO₂后肺癌终生危险度为2162／10⁶。吸入²³⁰PuO₂后死亡鼠肺癌累积发生率(F,％)与动物活存时问(T,天)及吸收剂量(D,Gy)三者的关系,可拟合为下列函数式：F=-1.35-0.069-1.58×10^-2D+(0.0236+2.18-10²D+1.68×10^-6D²)lnT 钚诱发肺癌的最短潜伏期为94天,11.3～17.6Gy可能是晟适致癌剂量。1只²³⁰PuO₂后37天死亡鼠,TLN发生原发性血管肉癌.     

Association of sedentary and physical activity time with maximal fat oxidation during exercise in sedentary adults

The present work examines the relationships of objectively measured sedentary time and physical activity (PA) with maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fat_max), in young and middle-aged men and women. A total of 121 young sedentary adults (81 women, age 22.1 ± 2.1 years, body mass index 25.2 ± 4.9 kg/m²) and 70 middle-aged sedentary adults (36 women, age 53.4 ± 4.9 years, body mass index 26.8 ± 3.8 kg/m²) participated in this cross-sectional study. PA was objectively assessed using a wrist-worn accelerometer for 7 consecutive days. Wrist accelerations were classified into sedentary time and PA of different intensity (light, moderate, vigorous, moderate-vigorous), taking into account age-specific cut-offs. MFO and Fat_max were determined for all subjects by indirect calorimetry, using a walking graded exercise test. No association was found between any of the sedentary time-related variables and MFO (all P ≥ .05). However, several sedentary time-related variables were related to FAT_max in young men and women (all P ≤ .04). A positive relationship was also detected between PA and MFO in young and middle-aged women (P ≤ .05), although this became non-significant after adjustment for cardiorespiratory fitness (P > .05). The present results suggest that, depending on the characteristics of the study cohort, sedentary time, and PA time may be related to MFO and FAT_max during exercise. Future longitudinal and intervention studies are warranted to better understand the role of sedentary time and PA in metabolic flexibility during exercise.     

Effect of age on visuomotor functional MR imaging

RATIONALE AND OBJECTIVES: We sought to determine the effect of age on functional MR imaging experiments performed with visual and motor stimulation. We hypothesized that there would be a diminution in the amplitude of fMRI activation with increasing subjects' age. MATERIALS AND METHODS: We used fixed effects models to study the amplitude of activation during a block design visuomotor task in three different age groups: old (mean: 75 years; standard deviation: 6 years), middle-aged (mean: 52 years; standard deviation: 9 years) and young (mean: 29 years; standard deviation: 5 years). Each group included 7 subjects. Regions of interest (ROI) were left primary motor area (LM1), supplementary motor area (SMA), and right and left occipital (RO, LO) visual areas. Individual subjects and group statistical parametric maps (SPMs) were generated for each ROI, and then the mean amplitude of activation was compared using the group analysis and t test. RESULTS: The young age group showed higher amplitude of activation than middle and old age groups in all ROI (P < 0.01 uncorrected). Unpaired two tailed t test results between the groups showed significant differences between middle and young, and old and young age groups in all ROIs (P < or = 0.05), with the exception of old and young age groups in RO region (P = 0.11). CONCLUSION: The group analysis, and unpaired t test results reveal higher amplitude of fMRI activation in the young versus the old and middle-aged groups.     

Age and controlled force exertion in Japanese women as measured by a computer-generated sinusoidal and quasirandom waveform display

Objectives

This study examined the relationship between age and controlled force exertion in 215 right-handed Japanese women aged 20 to 84 years, as measured in sinusoidal and quasirandom waveforms tasks.

Methods

The participants were divided into three groups based on age: 64 in the young group, 91 in the middle-aged group, and 60 in the elderly group. The participants adjusted their submaximal grip to the changing demand values, which were displayed as a sinusoidal or a quasirandom waveform on a computer screen. They performed the test three times. The evaluation parameters were the total differences between the demand values and grip exertion values.

Results

The coefficient of variance for both waveforms was in the same range for every age group, but the elderly group showed the highest value in the quasirandom waveform task. Significant correlations were found between the two waveforms in all three groups, and there were significant differences between the age groups. The elderly group scored higher than the middle-aged group, but there was no significant difference between the elderly and the young groups.

Conclusion

This study revealed a moderate relationship between the different age groups, and this relationship was significantly greater among the elderly than among the middle-aged women.     

Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men

We sought to test the hypothesis that brain blood flow and cerebral vascular responsiveness to carbon dioxide (CVR_CO2) are greater in aerobically trained young and old individuals compared to their untrained counterparts. In 11 young trained {[23 (20–26) years] [mean (95% confidence interval)]}, 10 young untrained [25 (22–28) years], 8 older trained [65 (61–69) years], and 9 older untrained [67 (64–71) years] healthy individuals, Doppler ultrasound of the internal carotid (ICA) and vertebral (VA) artery blood flow were determined, along with middle cerebral artery mean flow velocity (MCA V_mean). Bilateral ICA blood flow was higher in trained individuals when compared to untrained (≈31%, P < 0.05), but was not influenced by age. VA blood flow was not affected by age or cardiorespiratory fitness. MCA V_mean was reduced with age [59.5 (55.0–64.1) cm/s young vs 43.6 (38.4–48.9) cm/s old, P < 0.05] with no significant effect of training observed. MCA CVR_CO2 were not significantly affected by either age or training status, while ICA CVR_CO2 tended to be elevated in the old trained group. These findings indicate that endurance training enhances bilateral ICA but not VA blood flow in both young and older individuals.     

Age dependence of regional proton metabolites T2 relaxation times in the human brain at 3 T

Although recent studies indicate that use of a single global transverse relaxation time, T₂, per metabolite is sufficient for better than ±10% quantification precision at intermediate and short echo‐time spectroscopy in young adults, the age‐dependence of this finding is unknown. Consequently, the age effect on regional brain choline (Cho), creatine (Cr), and N‐acetylaspartate (NAA) T₂s was examined in four age groups using 3D (four slices, 80 voxels 1 cm³ each) proton MR spectroscopy in an optimized two‐point protocol. Metabolite T₂s were estimated in each voxel and in 10 gray and white matter (GM, WM) structures in 20 healthy subjects: four adolescents (13 ± 1 years old), eight young adults (26 ± 1); two middle‐aged (51 ± 6), and six elderly (74 ± 3). The results reveal that T₂s in GM (average ± standard error of the mean) of adolescents (NAA: 301 ± 30, Cr: 162 ± 7, Cho: 263 ± 7 ms), young adults (NAA: 269 ± 7, Cr: 156 ± 7, Cho: 226 ± 9 ms), and elderly (NAA: 259 ± 13, Cr: 154 ± 8, Cho: 229 ± 14 ms), were 30%, 16%, and 10% shorter than in WM, yielding mean global T₂s of NAA: 343, Cr: 172, and Cho: 248 ms. The elderly NAA, Cr, and Cho T₂s were 12%, 6%, and 10% shorter than the adolescents, a change of under 1 ms/year assuming a linear decline with age. Formulae for T₂ age‐correction for higher quantification precision are provided. Magn Reson Med 60:790–795, 2008. © 2008 Wiley‐Liss, Inc.     

Age-related white matter changes in high b-value q-space diffusion-weighted imaging

Introduction

To assess and compare age-related diffusion changes in the white matter in different cerebral lobes, as quantified by diffusion-weighted imaging (DWI) and high b-value q-space imaging (QSI).

Methods

Seventy-three cases without neurological symptoms or imaging abnormalities were grouped by age as young (<30 years, n?=?20), middle-aged (30–49 years, n?=?19), old (50–69 years, n?=?18), and very old (>70 years, n?=?16) and imaged by a 1.5-T MR scanner for DWI and QSI. Apparent diffusion coefficient (ADC) and mean displacement (MDP) values were calculated in the white matter of frontal, parietal, and temporal lobes and compared using Dunnett’s test, with the young group as a control.

Results

MDP values in frontal and parietal lobes were significantly higher in old and very old age groups than in the young, while those in the temporal lobes were significantly higher only in the very old group. ADC values were significantly higher in all three lobes in the very old group.

Conclusion

QSI is more sensitive than DWI to age-related myelin loss in white matter.     

Changes in markers of muscle damage of middle-aged and young men following eccentric exercise of the elbow flexors

It is well documented that unaccustomed eccentric exercise induces muscle damage, but the responses of middle-aged individuals to a bout of eccentric exercise have not been reported. The purpose of this study was to compare changes in indirect markers of muscle damage following eccentric exercise of the elbow flexors between 12 young (age: 19.4+/-0.4 years, height: 173.5+/-2.0cm, body mass: 65.8+/-3.5kg) and 12 middle-aged men (48.0+/-2.1 years, 169.5+/-1.7cm, 67.3+/-1.6kg). It was hypothesized that middle-aged men would be more susceptible to muscle damage than young men. All subjects performed six sets of five eccentric actions of the elbow flexors using a dumbbell of 40% of maximal isometric strength (MVC). Changes in MVC, elbow joint angles and range of motion, upper arm circumference, plasma creatine kinase activity and myoglobin concentration, and muscle soreness before, immediately after, and 1, 2, 3, and 4 days after exercise were compared between the young and middle-aged groups by a two-way repeated measures ANOVA. All criterion measures changed significantly (P<0.05) after exercise, but no significant differences in the changes in the measures except for muscle soreness were evident between groups. Development of muscle soreness after exercise was significantly (P<0.05) lower (approximately a half of the value) for the middle-aged group compared with the young group. These results did not support the hypothesis that middle-aged men would be more susceptible to muscle damage than young men.     

Proximale Tibiaepiphyse im Magnetresonanztomogramm

Background

The age estimation of living persons outside of criminal proceedings (e.g. in cases of refugees seeking asylum) has up to now been conducted voluntarily by means of physical inspection of signs of sexual maturity as well as through dental examination (without x-rays) due to legal reasons. Given the large variability of individual physical development the former method is particularly problematic for estimating age.

Samples and methods

Magnetic resonance imaging (MRI) of the right proximal tibial epiphysis was conducted on 41 young men aged 15–19 years from Hamburg and Schleswig-Holstein. The images were categorized according to the degree of maturity of the epiphysis (I: open, II: closed center, III: closed).

Results

The initial results suggest that the proximal tibial epiphysis in young men aged 15 years old is actively ossifying. In most cases this process is complete by the end of the 16^th year of life.

Conclusions

Should these results be confirmed after detailed validation studies it would open up the possibility to develop an additional method of age estimation in living persons (e.g., in refugee cases) using imaging which is non-invasive and with no exposure to radiation. This could also be a useful complementary tool within the currently available spectrum of methods for criminal proceedings.     

Decreased ankle and hip isometric peak torque in young and middle-aged adults with chronic ankle instability

ObjectivesTo compare ankle, knee and hip isometric peak torque between young and middle-aged adults with CAI, copers and un-injured controls.DesignCross-sectional.SettingResearch Laboratory.ParticipantsOne hundred fifty-six young and middle-aged adults with or without CAI volunteered.Main outcome measuresA handheld dynamometer measured isometric dorsiflexion, plantarflexion, knee extension, hip extension and hip abduction peak force during a 5 s trial. Average peak torque was calculated and normalized to body mass.ResultsA significant Age by Injury interaction for dorsiflexion suggest middle-aged un-injured controls (p < 0.001) and copers (p < 0.001) had lower isometric peak torque compared to their young adult counterparts, but there were no differences between young and middle-aged adults with CAI (p > 0.05). Significant Injury main effects suggest the CAI group had decreased plantarflexion (p = 0.004) and hip extension (p = 0.010) strength compared to un-injured controls, but not copers (p > 0.05). Significant Age main effects for all primary outcome measures were observed, indicating peak torque decreased with age (p < 0.05).ConclusionsRegardless of age, isometric ankle and hip peak torque was lower in participants with CAI compared to un-injured controls, but not copers. These findings provide further evidence towards the impact of CAI in both young and middle-aged adults.     

Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11–15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5×10⁷ colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg ^99mTc-DMP444 and two infected dogs with 37 MBq/kg ^99mTc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the ^99mTc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87±0.18 in endocarditis, 1.01±0.05 in non-infected controls and 1.09±0.02 in ^99mTc-IgG injected dogs (P<0.05). It is concluded that targeting activated platelets with the ^99mTc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake. Received 6 October and in revised form 27 December 1999