Intrasplenic blood cell kinetics in man before and after brief maximal exercise.

1. After a 4 min period of maximal exercise in 10 normal subjects (14 studies), there was a consistent decrease in total blood volume and a consistent increase in erythrocyte indices, which were maximal immediately after exercise. Peripheral platelet and leucocyte counts increased, but did not reach maximal values until 5-10 min after the end of exercise. 2. The distributions of 99mTc-labelled erythrocytes (five studies), 111In-labelled platelets (five studies) and 111In-labelled granulocytes (four studies) were monitored with a gamma-camera immediately after injection and before and after maximal exercise performed 60 min after injection. 3. Labelled erythrocytes equilibrated rapidly between the spleen and circulating blood after injection, whereas labelled platelets and granulocytes equilibrated more slowly. After exercise, each cell type was released from the spleen with a time course that was the reciprocal of the time course of the corresponding cell count in peripheral blood. Thus, whereas the radioactivity of 99mTc-labelled erythrocytes in the spleen, which fell to 0.46 (SD 0.09) of the pre-exercise value, increased towards its baseline value as soon as exercise was completed, the radioactivities of 111In-labelled platelets and 111In-labelled granulocytes decreased, to respective minimum values of 0.61 (0.09) and 0.63 (0.09) of the pre-exercise levels, 5-10 min after the end of exercise. The exercise-induced changes in lung radioactivity for each cell type, and their time courses, broadly reflected those in the corresponding cell counts in peripheral blood. Liver radioactivity tended to decrease for each cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte margination in the human lung and its response to strenuous exercise.

1. It is widely believed that the lung is an important site of granulocyte margination and releases most of the granulocytes of the peripheral neutrophilia of exercise. 2. We measured granulocyte margination in the lung in terms of the lung total blood granulocyte pool and the lung circulating granulocyte pool in eight patients without inflammatory disease or evidence of lung pathology by comparing the regional gamma-camera lung count rate of 111In-labelled granulocytes with that of 111In-labelled erythrocytes. According to the respective 111In activities in peripheral blood samples taken between 5 and 40 min after granulocyte injection, the lung marginating granulocyte pool was 0.78 (SEM 0.045) of the lung total blood granulocyte pool or 4.6 (0.92) of the lung circulating granulocyte pool 5 min after injection, decreasing to plateau values of 0.57 (0.053) and 1.53 (0.28) from 20 min after injection. This compared with corresponding whole-body ratios of about 0.6 and 1.5, respectively. 3. After 4 min of maximal exercise in four normal subjects given 111In-labelled granulocytes 60 min before exercise, the 111In-labelled granulocyte count rate over the lung increased to 1.23 (0.05) of the pre-exercise value with a time course that was essentially identical with the time course of the peripheral native neutrophilia. The spleen 111In signal decreased with the same time course, reaching a minimum of 0.63 (0.05) of the pre-exercise level at 5-10 min after the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of pulmonary embolism in elderly patients newly admitted to an acute geriatric unit: a prospective study.

To study the incidence of pulmonary embolism (PE) in elderly patients newly admitted to an acute geriatric unit, the authors carried out ventilation perfusion scans on 33 patients, 25 women and 8 men, mean age 79 years, consecutively admitted to the geriatric wards. The first scan was done within 5 days of admission and repeated between days 10 and 20. Where possible, patients with a positive second scan had a repeat scan at 2-3 months. Six (18%) patients were found to have a high probability of PE, 4 (12%) at the time of admission and two (6%) after admission. Three patients (9%) were considered to suffer from chronic pulmonary artery disease. Mortality was 5 for the whole group (15%) and 1 of 6 (17%) with a high probability of PE; this patient was suffering from carcinomatosis. The only patient who was anticoagulated suffered serious side effects. In no patient was PE clinically suspected. The authors conclude that PE is common in sick elderly patients newly admitted to acute geriatric wards, that rehabilitation with mobilization may precipitate new PE, and that nonanticoagulated PE does not seem to appreciably shorten the prognosis for life. Treatment with anticoagulants may be more dangerous than not treating PE in this older age group.

Spontaneous abrupt changes in the distribution of ventilation: a cause for apparent mismatching on ventilation/perfusion scintigraphy.

A defect seen in the perfusion scan in a region of lung that is normally ventilated is usually interpreted as indicating pulmonary vascular disease. Since the distribution of 99Tcm macro-aggregated albumin (MAA) represents the distribution of perfusion (Q) only at the time of MAA injection, the assumption is required that the distribution of ventilation (V) remains unchanged between MAA injection and the commencement of imaging. We report the V/Q scintigraphic findings in six patients (including four children), in whom this assumption could not be sustained. Thus ventilation imaged with 81Krm was seen to change during image acquisition in lobes that showed perfusion abnormalities. In some, but not all, views the appearances were typical for pulmonary vascular disease, which might easily have been misdiagnosed if the changes in the distribution of ventilation had not announced themselves by occurring during image acquisition. A ventilation image obtained immediately before injection of 99Tcm-MAA may be useful.

Distributions of an ultra-fine 99Tcm aerosol and 81Krm gas in human lungs compared using a gamma camera.

A 99Tcm aerosol of particle size 0.12 micron and the gas 81Krm were administered to four normal subjects and to eleven patients with airway disease. Posterior-anterior gamma camera images of erect lungs were compared qualitatively and quantitatively, and 99Tcm clearance rates were measured. Qualitatively the two images were similar in normal subjects but differed in most patients owing to small regions of high count density in the 99Tcm images. In a few patients, regional variations in ventilation were defined more finely by the aerosol. In both groups a significant vertical gradient in 99Tcm count density relative to 81Krm count density was found. Penetration of 99Tcm to the lung periphery relative to the hilar region was similar to that of 81Krm in the normal subjects and less than that of 81Krm in the patients. Possible causes of the differing distributions are discussed. The images obtained with the aerosol in the two groups studied were similar to those reported for larger particle aerosols.

Lung ventilation studies with technetium-99m Pseudogas.

Technetium-99m Pseudogas is an ultrafine near monodisperse aerosol of 0.12-microgram diam particle size. This report describes initial clinical experiences with 27 patients referred for investigation of suspected pulmonary embolism, and in whom Pseudogas ventilation images were compared with a high quality commercial aerosol. An additional group of ten patients with severe COPD was examined in a comparative trial of Pseudogas with 81mKr. Pseudogas was better than a conventional aerosol in reaching a diagnosis of pulmonary embolism using a simple blinded comparison with coded images. In addition, bronchial deposition was minimal unless COPD was severe. Moderately well patients had no difficulty inhaling the necessary activity in one or two breaths, and even severely ill and frail aged persons could accomplish the passive breathing maneuver in less than a minute. Clearance of Pseudogas was directly to the systemic circulation with a half-time of 10 min in normal subjects extending up to 100 min in patients with airways disease.

Investigations using an X-ray image intensifier and a TV camera for imaging transverse sections in humans.

A method for computed tomography using equipment available on some radiotherapy simulators has been investigated. An offset narrow fan beam of X rays passes transversely through the object and is continuously detected by an image intensifier and TV camera system while the beam and detector complete a rotation about the object in 30 seconds. Several TV lines of the images obtained at equal angular increments are digitised and summed to produce transmission projections from which a transverse section is formed by filtered back-projection. The dynamic range required of the camera is reduced by modifying the beam with a shaped metal filter. Images are produced without logarithmic processing or X-ray output calibration. Digital control circuitry is used for digitisation and spatial filtering, and a high-speed arithmetic array processor and digital frame store are used for back projection and image storage (Cynosure Imaging Systems Ltd.). Phantom studies using an object on a turntable with a stationary X-ray tube and intensifier showed the system to be capable of good spatial resolution and reasonable density resolution. Acceptable images of humans have been produced with the equipment added to a Ximascan simulator (TEM Instruments Ltd.). Radiation dose to the irradiated section can be as little as 200 microGy (20 mrad).

Measurements of regional ventilation using nitrogen-13 and krypton-81m in mechanically ventilated dogs.

13N2 and 81Krm were used to measure changes in upper/lower (U/L) ratios of regional ventilation in supine anaesthetised dogs mechanically ventilated at different tidal volumes and the results compared. Analysis of the slopes of the 13N2 washout curves indicated that U/L specific ventilation was less than unity at low tidal volumes and decreased as tidal volume increased. U/L total ventilation, measured using the specific ventilation results and estimations of relative lung using 13N2, also decreased with increase in tidal volume. Preferential distribution of ventilation to dependent lung regions thus increased with tidal volume despite the opposing hydrostatic forces from the abdomen. Regional count density distributions in 81Krm images of the lungs were analysed. At high specific ventilation rates, correction of 81Krm count density is required in order to obtain correct regional ventilation information. The specific ventilation rates in this series were such that the uncorrected U/L count ratios of 81Krm increased as tidal volume increased in contrast to the decrease in U/L total ventilation recorded by the 13N2 method. When corrections using the 13N2 specific ventilation results were applied, the changes in U/L 81Krm count ratios with tidal volume showed a similar trend to the changes in total ventilation measured with 13N2. Sources of error in the two techniques are briefly discussed.

Preservation of the pulmonary vasoconstrictor response to alveolar hypoxia during the administration of halothane to dogs.

The action of halothane on the pulmonary vasoconstrictor response to unilateral alveolar hypoxia was studied in two groups of dogs. In the first group the redistribution of blood flow between the two lungs was studied with a radioactive isotope method, which provided intermittent measurements, whilst in the second group the distribution of blood flow was observed continuously. In both groups there was no significant alteration of the hypoxic vasoconstrictor response with inspired halothane concentrations varying from 0.5 to 1.5%.

Indium-111-labeled autologous leukocytes in man.

Autologous leukocytes have been isolated, labeled with indium-111, and administered to 15 patients suspected of inflammatory disease. The stability of the label has been demonstrated and the in vivo kinetics and distribution of the labeled cells studied. The distribution is influenced by the type and viability of the cells separated by three different techniques. Generally, there was initial accumulation of radioactivity in the lungs; approximately half of this cleared in 15 min and the remainder slowly. Twenty-five to 50 percent of the radioactivity subsequently distributed in the spleen, liver, and bone marrow, and these did not show significant change with time up to 48 hr post injection. The In-111 radioactivity administered as labeled leukocytes free from erythrocytes cleared from the circulating blood with a half-time of 7.5 hr. In three of 15 patients, the suspicion of inflammatory disease could not be confirmed, and in these a normal distribution of radioactivity was observed. In the remaining 12 patients, focal accumulation of radioactivity was detectable within 4 to 24 hr after administration, and subsequent confirmation of sepsis was obtained. From three such patients, samples of abscesses were recovered which showed markedly higher radioactivity than that in the same weight of blood.

Kinetics of indium-III labelled lymphocytes in normal subjects and patients with Hodgkin's disease.

The distribution in the body and the circulation in the blood of autologous lymphocytes labelled with indium-III were studied in two normal subjects and two patients with Hodgkin's disease. Four hours after injection radioactivity was identified in the spleen, liver, and bone marrow. Radioactivity, followed by imaging and whole body scanning, began to appear in the lymph nodes four to 18 hours after injection, and some, though not all, lymph node groups in the body could be readily visualised. There were no differences between the normal subjects and the patients with Hodgkin's disease. The pattern of clearance of radioactivity from the blood was consistent with a normal circulation between blood and lymphoid tissues of the labelled lymphocytes. Since indium-111 stays firmly attached to the cell, it seems an ideal label for studying lymphocyte kinetics, and the use of this technique may have further clinical application.

Indium-111-labelled leucocytes for localisation of abscesses.

Leucocytes from eight patients who were thought to have an abscess were labelled with indium-111 and reintroduced into the circulation. The distribution of radioactivity was followed by whole-body scanning and imaging with a gamma camera. Focal accumulation of radioactivity were observed in the lesion in the three patients with abscesses, in the lungs of a boy with bacterial endocarditis, in the knee of a woman with rheumatoid arthritis, and at the site of intramuscular injections in another patient. The use of radiolabelled cells for the detection of focal pathological processes would seem to be an important addition to conventional diagnostic methods.

Measurement of an index of muscle capillary permeability and its correlation with serum insulin values in maturity-onset diabetic subjects.

1. An index of capillary permeability was obtained by measuring the ratio of the clearance rate of 77Br to that of 133Xe in the anterior tibial muscle, after a short period of maximal ischaemic exercise. 2. Seventeen control subjects and thirty-two maturity-onset, non-insulin-treated diabetic subjects, aged 60 years or less, were studied. Short glucose tolerance tests were performed in the diabetic subjects during which blood sugar and serum insulin concentrations were estimated. 3. The 77Br/133Xe clearance ratio was increased in the diabetic subjects compared with the control subjects. In the diabetic subjects, there was an inverse correlation between the insulin at 60 min after glucose and the 77Br/133Xe clearance ratio. There was also a direct correlation between the 77Br/133Xe clearance ratio and the age of the patient in the diabetic group but not in the control group. 4. The results demonstrate that a reduced insulin response to oral glucose is associated with increased capillary permability and may play a role in the development of microangiopathy.

Reduction of hypoxic pulmonary vasoconstriction during trichloroethylene anesthesia.

A double-lumen tube was inserted into the trachea of dogs anesthetized with intravenous pentobarbital (30-40 mg/kg). Blood flow/unit lung volume in each lung was measured with 133Xe. Both lungs were initially ventilated with oxygen and measurements of pulmonary blood flow, CO2 output, cardiac output, and blood gases were made. When nitrogen was administered to one lung blood flow was diverted to the opposite lung. The diversion of flow was reduced by the inhalation of 1% trichloroethylene but returned after withdrawal of the anesthetic. There were no significant changes in cardiac output. Changes in CO2 output and arterial Po2 were compatible with the xenon results. It is concluded that trichloroethylene may increase arterial hypoxemia by reducing vasoconstriction in hypoxic areas of lung.

Thrombin-induced disseminated intravascular coagulation in the dog. I: Demonstration of microthrombi in lung.

Disseminated intravascular coagulation was induced in dogs by the infusion of a fibrinolytic inhibitor followed by thrombin. The deposition of microthrombi in the lung was demonstrated by radioactive labelling of platelets and fibrinogen.

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.