Positron Emission Tomography in Tumor Diagnosis and Treatment Follow-Up

The technique of positron emission tomography (PET) is described. PET is an in vivo imaging and quantitative technique which allows the visualization of various functional and biochemical parameters. PET is a tracer technique in which bioactive tracer substances are labelled with short-lived positron emitting radionuclides. The most important of these are ¹⁵O, ¹³N, ¹¹C and ¹⁸F with decay times ranging from 2 min to 2 h. The radiolabeled substance is injected intravenously and the distribution, uptake and binding are registered externally with the PET camera using of the order of 4 000 small detectors. The camera produces simultaneously 15 tomographic slices in which the absolute concentration of the tracer substance can be measured. Using a dynamic imaging sequence starting after the injection of the tracer, the dynamics of the tracer uptake is recorded and can be used to deduce functional parameters, such as perfusion flow, tracer distribution, binding to receptor or enzyme systems, etc. depending on the choice of tracer substance. The great versatility of PET and its potential of direct noninvasive study of tumor function will make it a very important clinical and research tool in oncology. With the choice of substances selective for a certain aspect of a tumor's biochemistry the potential opens for a better diagnosis, improved differential diagnosis and, especially with the use of metabolic tracers, an improved possibility to evaluate the response to treatment.     

Activity-dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.     

Intracarotid histamine administration results in dose-dependent vasogenic brain oedema formation in new-born pigs

Inflammation Research -     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Interaction between sleep and growth hormone

The relation between nightly growth hormone (GH) secretion and sleep is poorly understood. To examine whether disturbances in GH secretion are reflected in abnormal sleep patterns 8 subjects with isolated GH deficiency and 9 subjects with excess of GH (acromegalics) underwent all night sleep studies, polysomnography. Moreover, the effect of correcting GH concentration on sleep patterns were examined in the same subjects. The results showed that all subjects with GH disturbances had abnormal REM and delta sleep and normalization of GH concentration was followed by correction of the sleep stages. By power spectrum analysis of the sleep EEG it was showed that during low GH concentration the sleep energy was low, and high GH concentration was associated with high sleep energy, and correction of abnormal plasma GH levels resulted in normalization of REM and delta sleep energy per time unit.     

A method for monitoring intracerebral temperature in neurosurgical patients

Current interest in brain temperature and selective brain cooling makes a method allowing for continuous monitoring of intracerebral temperature in humans desirable. The authors describe a safe, simple, and reliable technique using a thermocouple of copper and constantan in combination with intraventricular monitoring of intracranial pressure for measurement of brain temperature in neurosurgical patients.     

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.     

Anabolic and catabolic hormonal response of elite runners to training at high altitude

A 2-week training period 2000 meters above sea level performed by 6 male elite Swedish runners influenced neither basal anabolic (total and non-sex hormone-binding globulin (SHBG)-bound testosterone (NST) and insulin-like growth factor-1 (IGF-1) nor catabolic (cortisol) hormones when comparing serum levels prior to and after the training camp. The anabolic vs catabolic hormone balance, expressed as the NST: cortisol ratio, also remained unchanged as well as SHBG and body mass. Thus, training at 2000 meters above sea level, often practised by elite runners to improve performance in competition at sea level, does not result in a catabolic situation after return to sea level, as measured by peripheral hormones. However, the adaptation to high altitude was associated with a slight (NS) decrease in testosterone as well as in anabolic vs catabolic balance as measured the third day at high altitude. Simultaneously, a decrease in subjective performance was claimed by the runners, but could not be shown by objective measurements. From day 3 to day 9 at high altitude, all runners claimed a subjective recuperation of performance. Total and non-SHBG-bound testosterone increased significantly from day 3 at high altitude to the first post-camp sea-level test. The results reflect the necessity of adaptation when travelling to races at different altitudes. The Swedish runners had significantly higher cortisol, total testosterone and NST levels compared with basal values of a group of 17 elite Kenyan runners living and training at high altitude. Since the NST cortisol and IGF-1 values were not lower, a catabolic state or malnutrition was not likely to be present. The results might reflect an adaptation to altitude or ethnic variations.     

The effects of training, immobilization and remobilization on musculoskeletal tissue

Compared with the knowledge on immobilization, the effects of remobilization on musculoskeletal tissues have not been well established. What is sure is that remobilization and rehabilitation of any component of the musculoskeletal tissues require much more time than the time needed to cause the immobilization atrophy. With intensive rehabilitation, the functional properties of skeletal muscles can be improved significantly even years after the injury and following immobilization, but no study has shown whether full recovery is possible and whether these rehabilitated muscles are able to respond normally to further training. Experimental studies have given evidence that slow-twitch muscle fibres have better capacity for recovery than fast-twitch fibres, most likely due to better circulation and higher protein turnover. Also evidence has been given that fibre regeneration is possible through satellite cell activation and myotube formation. Very little is known, however, about the effects of age, gender or the level of preimmobilization muscle performance on the restoration capacity. Also the fate of the marked structural changes (for example, connective tissue accumulation) induced by immobilization is unknown. Tendon and ligament tissues are likely to respond appropriately to remobilization, resulting in acceleration of collagen synthesis and fibril neoformation. However, there is a strong suspicion that remobilized tendons and ligaments will not achieve all the biochemical and biomechanical properties of their healthy counterparts. Specifically, the amount of weak type III collagen has been shown to be overrepresented in these tissues instead of mature, strong type I collagen. It is not known whether this is an important risk factor for ruptures during later activity. The effects of remobilization on muscle-tendon junction and proprioceptive organs are not known. It would not be surprising if the serious structural changes induced by immobilization were unrestorable. In the literature dealing with immobilization and remobilization, cartilage degeneration is always a major concern, because not only too strenuous training or immobilization, but also unskilful remobilization may activate this process leading finally to osteoarthrosis. Bone may be one of the best components of musculoskeletal tissues to respond to remobilization, probably because the immobilization atrophy of bone is largely quantitative (osteoporosis) only. The prerequisites for bony recovery are that the follow-up time is long enough (months) and that immobilization has not exceeded about 6 months, the time limit between active and inactive (irreversible) osteoporosis. Prevention of the atrophying effects of immobilization can be very successful if performed properly. According to present knowledge, there are many methods for the purpose, including preimmobilization training early, controlled mobilization; optimal positioning of the immobilized joint; muscular training during immobilization; early weightbearing; exercise with the nonimmobilized extremity; and electrical stimulation. Lots of education and information will be needed, however, before these methods are deeply rooted in the daily routines of the attending physicians, physical therapists, athletic trainers and other persons involved in the treatment of musculoskeletal problems.