New lessons from the atomic bomb survivors.
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Biomedical subjects
Publications and source records attributed to J S Orr.
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The results of NMR examinations in 52 patients with histological or clinical diagnoses of cerebral tumor are reviewed. An increase in relaxation time was recognized in all tumors but problems were experienced in distinguishing the margin of tumors from surrounding edema. Mass effects were well demonstrated as a result of the high level of gray-white matter contrast available with inversion-recovery sequences and the use of coronal and sagittal imaging planes. In general repeated FID sequences were less sensitive in detecting tumors than inversion-recovery or spin-echo sequences. Periventricular edema was well demonstrated with spin-echo sequences and was of importance in recognizing acute or subacute hydrocephalus. Radiation therapy was associated with increased relaxation times particularly within white matter. Problems in the recognition of tumor recurrence following treatment are outlined. The opportunities and challenges that NMR imaging is now providing for physicists and radiologists are discussed.
Lipogenic rates (measured with 3H2O) in hepatocytes from fed or starved euthyroid rats were similar in magnitude to those measured in livers in vivo. Hepatic lipogenesis in vivo in fed triiodothyronine (T3)-treated rats was greater than in fed control rats, but rates in vitro were only 16% of those of control rats. It is concluded that hepatic lipogenesis in vivo in T3-treated rats utilizes precursors from extrahepatic tissues. Glycogen depletion of hepatocytes from fed control rats decreased lipogenesis, and rates were then similar to those in hepatocytes from fed T3-treated rats. Addition of lactate (2 mmol/l) and pyruvate (0.2 mmol/l) had little stimulatory effect on lipogenesis in hepatocytes from fed control rats, but increased lipogenesis in glycogen-depleted hepatocytes (by 86%), hepatocytes from starved rats (by 25%) and hepatocytes from T3-treated rats (by 60%). In the presence of lactate and pyruvate, 3-mercaptopicolinate (3-MPA) (an inhibitor of gluconeogenesis) did not affect lipogenesis in hepatocytes from fed control rats but substantially increased lipogenesis in hepatocytes from starved euthyroid rats or fed hyperthyroid rats. Thus, in hepatocytes from starved euthyroid rats or fed hyperthyroid rats gluconeogenesis competes with lipogenesis for available precursors (lactate and pyruvate). In contrast, in fed rats carbon flux is predominantly towards lipogenesis. Effects of 3-MPA in the presence of lactate and pyruvate were much less in glycogen-depleted cells from fed rats than in hepatocytes from starved or T3-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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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).
The two strands of the problem are the shapes and changes with time of cell survival curves on the one hand and the responses of cell constituents to radiation on the other. Evidence of correlations between results of studies of these two types of phenomena under the influence of a wide range of modifying agents is required to establish mechanisms. Recovery may be defined as referring to the whole cell, while repair should be regarded as a process carried out by one substance on another. The degrees of usefulness and possible deficiencies of a multi-hit/target model and a repair model for explaining cell survival curves and cell recovery are compared in a range of circumstances. A fully satisfactory model is not yet available.
Nuclear magnetic resonance (NMR) has begun to be applied to a variety of clinical situations. The present status of the technology and some current patient data are discussed and reviewed.
Possible effects of adrenaline, noradrenaline, vasopressin, and angiotensin II to increase 14CO2 production from [1-14C]oleate were examined in hepatocytes from fed L-triiodothyronine (T3)-treated or control rats. Rates of 14CO2 production were decreased and rates of ketogenesis increased in hepatocytes from T3-treated rats. These changes were accompanied by a marked shift of the 3-hydroxybutyrate:acetoacetate concentration ratio towards acetoacetate. Rates of glucose and lactate release were decreased. Whereas the Ca2+-mobilizing hormones increased 14CO2 production from [1-14C]oleate by 64-84% with hepatocytes from control rats, they increased 14CO2 production from [1-14C]oleate by on 24-32% with hepatocytes from T3-treated rats. The magnitude of the response to the Ca2+-mobilizing hormones in hepatocytes from T3-treated rats was increased by the addition of 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, to the incubation medium (increases of 52-88%). In the presence of 3-mercaptopicolinate, the 3-hydroxybutyrate:acetoacetate concentration ratio in hepatocytes from fed, T3-treated rats was similar to that in hepatocytes from control rats in the absence of 3-mercaptopicolinate. The results demonstrate that hyperthyroidism per se does not lead to a loss of sensitivity, in terms of oleate oxidation, either to the catecholamines or to vasopressin and angiotensin II. The impaired ability of hepatocytes from T3-treated rats to respond to these hormones is a consequence of decreased net glycolytic flux or a more oxidized mitochondrial redox state.
The results of nuclear magnetic resonance (NMR) examinations in 26 patients with histologic (15 cases) or clinical (11 cases) diagnoses of tumors within the posterior fossa were reviewed and compared with x-ray computed tomography (CT). Most tumors displayed an increase in T1 and T2 relative to brain. All seven benign tumors were seen with both CT and NMR, although one of these cases initially was misdiagnosed on the basis of the CT findings. The extent of these tumors was equally well shown with CT and NMR in three cases but was demonstrated better by NMR in four. Calcification was seen with CT but not with NMR in two of these patients. All 19 malignant tumors were demonstrated with NMR. Two of these were not seen with CT. In 12 patients minimal changes consisting of a poorly defined low-attenuation are or minor displacement of the fourth ventricle were noted with CT, although much more extensive changes were seen with NMR. In three patients the changes were equally well shown with both techniques. In the remaining two cases, the extent of the tumor was defined more accurately with contrast-enhanced CT, where the margin between tumor and surrounding edema was better seen than with NMR. Mass effects were better demonstrated with NMR in 13 patients and equally well shown in six. Bony erosion was better demonstrated with CT in two cases. Hydrocephalus with periventricular edema was seen in five patients; in each it was more clearly demonstrated with NMR. The NMR diagnosis of tumors is discussed and relevant new developments are summarized.
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A nuclear magnetic resonance (NMR) imaging system is described, and preliminary results from its clinical use are presented. The properties and detection of the magnetisation due to hydrogen protons are outlined, and a rotating frame is introduced to describe the motion of the magnetisation. Radiofrequency (RF) pulses are used to rotate the magnetisation, and slice selection is achieved using a 90 degree RF pulse and a magnetic field gradient. Data acquisition and image reconstruction are explained. Three scanning sequences are described: repeated free induction decay (FID), inversion - recovery, and spin-echo. These sequences produce images whose pixel values have different dependencies on hydrogen proton density, T1 and T2. Inversion-recovery images show striking differentiation between grey and white matter in the brain. The absence of bone artifact is a significant advantage over X-ray computed tomography in the posterior fossa, where rapid repeated FID sequences can also be used to demonstrate flow effects. The considerable soft tissue contrast available with NMR is of value in demonstrating disease within the liver where T1 appears to be sensitive but relatively nonspecific diagnostic parameter. High resolution scans are of value in demonstrating the adrenal gland and spinal cord.
A nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd was used to produce tomographic images of the brain in eight volunteers and fourteen patients. The use of an inversion recovery technique designed to emphasise variations in the spin-lattice time constant (T1) resulted in remarkable differentiation between grey and white matter in all subjects examined. White matter was seen both centrally and peripherally to subcortical level and the basal ganglia were clearly demarcated by the surrounding white matter and ventricular system. The posterior fossa was visualised with substantially less artefact than with X-ray computed tomography (CT) and both the brainstem and middle cerebellar peduncle were clearly shown. Pathological appearances in patients with glioblastoma multiforme, cerebral infarction, and cerebral aneurysm were demonstrated and compared with those seen with CT. The technique will require thorough clinical evaluation but appears to have considerable potential in the diagnosis of neurological disease.
Posterior fossa scans were performed on five healthy volunteers using a nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd. Three different NMR scanning sequences were used. In the first, a type of saturation-recovery technique was used to produce images strongly dependent on the density of hydrogen nuclei, but with some dependence on the spin-lattice relaxation time (T1). In the second, an inversion-recovery technique was used to produce images with a stronger dependence on the spin-lattice relaxation time. In the third, a spin-echo technique was used to obtain images with a dependence on the spin-spin relaxation time (T2). All three types of NMR image were unaffected by bone artifact. Visualization of brain adjacent to the skull base was obtained without loss of detail due to partial-volume effect from bone. The saturation-recovery images highlighted arteries and veins that were clearly visible without the use of contrast agents. The inversion-recovery images showed remarkable gray-white matter differentiation enabling internal structure to be seen within the brainstem and cerebellum. The trigeminal nerve and ganglion were also seen outside the brain. Experience with the spin-echo technique is limited, but the images at the base of the brain show considerable soft-tissue detail. The NMR images of the posterior fossa in this study were comparable in quality to those obtained from a new rotate-rotate x-ray computed tomography machine and were superior in several respects.