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Biomedical subjects

A Lilja

Publications and source records attributed to A Lilja.

At least 19 recordsLinked to original sources

Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar--a blinded, prospective randomized study.

PURPOSE: To describe and explore the relationships between pain, emotional state and coping strategies in patients with chronic radicular neck pain before and after surgery or conservative treatments. METHODS: We randomize 81 conseutive patients with cervical radicular pain and nerve root compression, verified by MRI, to either surgical decompression with fusion or physiotherapy or neck collar. Emotional state was both measured with Mood Adjective Check List. Hospital Anxiety and Depression Scale and with a Coping Strategies Questionnaire. Pain was measured with VAS and function with Disability Index Rating. Measurements were made before treatment, and follow ups after 3 and 12 months post treatment. RESULTS: We found generally a low emotional state with anxiety, depression and sleep-disturbances not only connected to pain. Pain improved faster in the surgery group but after one year no differences were seen. Surgery and physiotherapy improved function with heavy work compared to collar after 3 months. Many patients used active coping before treatment, but after treatment more passive coping strategies were found. CONCLUSION: We recommend a multidisciplinary rehabilitation with cognitive behavioural therapy and psychological interventions.

Adaptation, Psychological↗

Expression of the IL-6 family cytokines in human brain tumors.

In our RT-PCR screen for cytokine expression in human brain tumors we discovered increased levels of oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), all belonging to the interleukin-6 (IL-6) cytokine family, in most of the tumors. The expression of these cytokines in normal adult brain tissue was found to be very low or below detection limit. OSM expression was elevated in most of the tumors and immunohistochemistry analysis showed that the tumor cells contained OSM in their cytoplasm, suggesting they produce this factor. Overexpression of OSM has not previously been reported in primary human brain tumors. The IL-6 cytokine family acts through a common gp130 receptor subunit that activates the JAK/STAT signaling pathway and therefore they have been suggested to have overlapping effects. Tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase 1 (MMP-1) and MMP-3 and IL-6 have been reported to be regulated by OSM. IL-6 was low or absent in the tumors. TIMP-1, MMP-1 and MMP-3 was expressed in most tumors but with no strict correlation to OSM levels.

Astrocytoma↗

Meningioma treated with interferon-alpha, evaluated with [(11)C]-L-methionine positron emission tomography.

PURPOSE: In meningioma patients with postoperative residual masses, recurrent or primarily inoperable tumors, positron emission tomography (PET) with [(11)C]-L-methionine was used to evaluate treatment efficacy of IFN-alpha. EXPERIMENTAL DESIGN: Twelve patients were treated with IFN-alpha at a dose of 1.5-5 million IU s.c. daily. PET, computed tomography, and/or magnetic resonance imaging were performed in all patients before and, at regular intervals, during IFN-alpha treatment. The ratio of tumor hot-spot uptake to cerebellar uptake or to cortex uptake was calculated. This ratio estimates the relative methionine accumulation in the tumor and presumably the proliferative activity in the tumor. RESULTS: During IFN-alpha treatment, PET demonstrated a mean relative percentage of reduction in the uptake ratio (MRelR) of 22.3% in the meningiomas. In nine patients who were considered responders, defined as patients with a positive MRelR, the MRelR was 30.4%. For the three nonresponders, defined as patients with a negative MRelR, the MRelR was -1.8%. Three patients were followed for a long time: two patients for 8 years and one patient for 4 years and 6 months; the two patients followed for 8 years are still on IFN. The volumes of these tumors were constant or showed a slight decrease. No correlation was found between histopathological diagnosis (PAD) WHO grading I-III of meningiomas and response to IFN-alpha treatment. CONCLUSIONS: PET was judged a useful method to predict which patients are suitable for long-term treatment with IFN-alpha and also for dose finding. In five patients treated from 9 months to 8 years, IFN-alpha seemed to be an effective oncostatic drug. The clinical usefulness of IFN-alpha, taking adverse reactions into account, must be evaluated in a larger series of patients.

Adult↗

Evaluation of the effect of high-energy proton irradiation treatment on meningiomas by means of 11C-L-methionine PET.

A remnant meningioma of WHO grade I that is located at the base of the skull and is treated with radiotherapy has to be followed up for at least 5-10 years to evaluate the treatment effect and detect recurrence. The tumour has to grow considerably to show detectable volume increase on computed tomography (CT) or magnetic resonance imaging (MRI). Owing to the location at the base of the skull, a small increase in tumour volume may be hazardous. It is thus important to find a method to evaluate treatment effects earlier and potentially detect those tumours that have a tendency to grow. Nineteen patients with intracranial meningiomas were given irradiation with the 180-MeV proton beam at the Svedberg Laboratory, Uppsala, Sweden. The fractionation schedule used was in general a total dose of 24 Gy in four consecutive daily 6-Gy fractions. Serial 11C-Lmethionine PET examinations were used to evaluate the effect of stereotactic proton beam treatment. The radioactivity uptake in the tumour was evaluated as the ratio to the uptake in normal brain tissue. The follow-up period thus far is 36 months. In 15 of the 19 patients, 11C-L-methionine uptake was reduced 36 months after irradiation compared with the pre-treatment uptake of the tracer. In the total patient group the average reduction was 19.4%. Our results reveal that proton beam irradiation of meningiomas had an inhibitory effect on the methionine uptake in the meningiomas, although tumour size remained unchanged. The combination of unchanged tumour morphology and a reduction in methionine uptake after irradiation suggests that 11C-L-methionine PET might enable earlier evaluation of the treatment effect than is possible with CT or MRI.

Adult↗

Cognitive functioning and cerebrospinal fluid concentrations of neuropeptides for patients with good neurological outcomes after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Many patients exhibit cognitive disturbances after aneurysmal subarachnoid hemorrhage (SAH). Structural and functional neuroimaging has failed to demonstrate any correlation with these complaints. This study was performed to investigate whether neuropeptide concentrations in cerebrospinal fluid could be related to cognitive disturbances after SAH. METHODS: Lumbar cerebrospinal fluid was obtained, 3 to 6 months after surgery, from 17 patients who experienced good outcomes after aneurysmal SAH. The samples were analyzed for various neuropeptides using radioimmunoassays, and the peptide concentrations were evaluated in relation to scores on standardized neuropsychological tests. RESULTS: The neuropsychological test results were normal for eight individuals, whereas the remaining nine patients exhibited various degrees of cognitive impairment. There was no correlation between the concentrations of arginine vasopressin or neuropeptide Y and test performance. However, significant correlations between cognitive impairment and elevated levels of beta-endorphins (P = 0.02), corticotropin-releasing factor (P = 0.004), and delta sleep-inducing peptide (P = 0.045) were noted. CONCLUSION: Patients with cognitive impairments after aneurysmal SAH exhibited higher cerebrospinal fluid concentrations of endorphins, corticotropin-releasing factor, and delta sleep-inducing peptide than did those with normal capacity. This is probably attributable to diffuse derangement of transmitter release in the brain, resulting from the insult or ensuing complications, although a secondary increase in corticotropin-releasing factor concentrations caused by increased stress during the testing because of reduced cognitive capacity cannot be excluded.

Adult↗

Aggression: destructive and constructive aspects.

The concept of aggression was long relegated to the shadow of the libido in psychoanalytic theory, placed among the negative affects by some theoreticians, denied the role of a primary drive among leading writers in clinical psychology, brought to the fore as an adaptive force in ethology, and proved to be a decisive factor in the development of psychosomatic ailments. The second part of the paper reviews experiments using projective techniques, showing that highly creative subjects as opposed to ones low in creativity seem inclined to accept their aggressive impulses. A total denial of these impulses has been typical of women with breast cancer.

Adolescent↗

Stereotactic irradiation of skull base meningiomas with high energy protons.

Nineteen patients with inextirpable skull base meningioma with involvement of neurovascular structures were given irradiation with a 180 MeV proton beam at the The Svedberg Laboratory, Uppsala, Sweden. The patients were treated seated in a fixed position with a stereotactic approach. Titanium-markers to the outer table served for identification and verification of the target positioning for dose planning and irradiation. The patients were given a total dose of 24 Gy in four consecutive daily 6 Gy fractions. All patients have been followed for at least 36 months. So far no meningiomas have progressed after treatment. Two patients have developed corticosteroid responsive oedema in the target area 6 moths after treatment. Late, but not serious, symptoms of side effects have been observed in one patient.

Adult↗

Frontal lobe dysfunction in patients with non-frontal malignant gliomas: a monoaminergic dysregulation?

Previous investigations concerned with the neuropsychological function of patients with intracerebral supratentorial malignant gliomas has revealed the frequent occurrence of signs suggestive of an inhibitory frontal lobe dysfunction regardless of the intracerebral localization of the tumor and before the diagnosis was known to either the investigator or the patient. Upon closer analysis, the frontal lobe dysfunction has been verified by the demonstration of reduced blood flow in frontal areas in these patients. Since many of the findings can be related to a dysfunction of dopaminergic neurotransmission, we hypothesize that abnormal astrocytes interfere with the metabolism, transport and release of various neurotransmitters of which dopamine may be the one responsible for the most striking neuropsychological abnormalities in patients with malignant gliomas.

Animals↗

Long-term tacrine treatment in three mild Alzheimer patients: effects on nicotinic receptors, cerebral blood flow, glucose metabolism, EEG, and cognitive abilities.

The effect of long-term treatment with tacrine (tetrahydroaminoacridine) was studied in three Alzheimer patients (aged 57, 64, and 68 years) with mild dementia. All three patients had a Mini-Mental State Examination score of 24/30 and carried at least one apolipoprotein E (ApoE) epsilon4 allele. Tacrine was given in doses between 80 and to 160 mg daily for 13-31 months. A lower tacrine concentration was observed generally in cerebrospinal fluid (CSF) compared with plasma. The acetylcholinesterase activity in CSF tended to be increased following longer periods of tacrine treatment, whereas the butyrylcholinesterase activity was decreased. The three patients repeatedly underwent positron emission tomography investigation of cerebral blood flow, nicotinic receptors, cerebral glucose metabolism, and electroencephalogram (EEG) and cognitive tests. Positive influences on these parameters were observed following both short-term and long-term treatment with tacrine. Improvement of nicotinic receptors (measured as 11C-nicotine binding), cerebral blood flow, EEG, and some cognitive tests (trail making test, block design test) occurred earlier after initiation of tacrine treatment compared with the glucose metabolism, which was increased after several months of tacrine treatment. An improvement in attention (trail making test) was observed following tacrine as sign for frontal lobe activation (EEG). The functional effects of tacrine in Alzheimer patients appeared to be related to both dose and length of cholinesterase inhibitor treatment.

Aged↗

Brain networks affected by synchronized sleep visualized by positron emission tomography.

Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and positron emission tomography (PET). Scanning was performed during wakefulness and after the subjects had fallen asleep. Sleep stage was graded retrospectively from electroencephalogram (EEG) recordings, and scans were divided into two groups: wakefulness or synchronized sleep. Global flow was quantified, revealing no difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way analysis of variance (ANOVA) was performed after correcting for differences in anatomy and global flow. The sum of squares of the z-score distribution showed a highly significant (P < 0.00001) omnibus difference between sleep and wakefulness. The z-score images indicated decreased flow in the thalamus and the frontal and parietal association cortices and increased flow in the cerebellum during sleep. A principal component (PC) analysis was performed on data after correction for global flow and block effects, and a multivariate analysis of variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep and revealed distinct networks consisting of PC 2, cerebellum and frontal and parietal association cortices, and PC 5, thalamus.

Analysis of Variance↗

Temporal lobe epilepsy visualized with PET with 11C-L-deuterium-deprenyl--analysis of kinetic data.

OBJECTIVES: The purpose of the study was to develop a simplified method for the acquisition and analysis of data from positron emission tomography (PET) using the ligand 11C-L-deuterium-deprenyl. This is motivated by an increased interest in methods to characterize gliosis in neurodegenerative diseases and epilepsy, which can be defined due to an increased expression of the enzyme MAO-B. METHODS: Seven patients with temporal lobe epilepsy were investigated with PET. The tracer kinetics in different brain structures was recorded and analyzed using different models with and without a plasma input function. The derived values were correlated to literature values of 3H-deprenyl binding in frozen sections from normal human brains. RESULTS: A good correlation was seen between in vivo binding and in vitro data, with the correlation being equally good irrespective of whether metabolite corrected plasma or modified cerebellar uptake values were used as input function. The epileptic lobe was, compared to non-epileptic, characterized by a lower initial distribution and an enhanced late accumulation of the tracer. With the applied method, it was possible to correctly identify the epileptic side in all 6 unilateral patients and I probable bilateral case. CONCLUSIONS: PET with 11C-L-deuterium-deprenyl gives a good correlation between calculated in vivo binding and MAO-B activity. The analysis can be simplified and blood sampling avoided if modified cerebellar time-activity data is used as a reference. Separate images of distribution volume and MAO-B binding can be generated.

Adult↗

Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors.

PURPOSE: Carcinoid tumors, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP). We have evaluated the usefulness of positron emission tomography (PET) with carbon-11-labeled 5-HTP in the diagnosis and treatment follow-up evaluation of patients with neuroendocrine tumors. PATIENTS AND METHODS: PET using 11C-labeled 5-HTP was compared with computed tomography (CT) in 18 patients (14 midgut, one foregut, one hindgut carcinoid, and two endocrine pancreatic tumors [EPT]). In addition, 10 of 18 patients were monitored with PET examinations during treatment. RESULTS: All 18 patients, including two with normal urinary 5-hydroxyindole acetic acid (U-5-HIAA), had increased uptake of 11C-labeled 5-HTP in tumorous tissue as compared with normal tissue. Liver metastases, as well as lymph node, pleural, and skeletal metastases, showed enhanced 5-HTP uptake and PET could detect more lesions than CT in 10 patients and equal numbers in the others. Tumor visibility was better for PET than for CT due to the high and selective uptake of 5-HTP with a high tumor-to-background ratio. Binding studies indicated an irreversible trapping of 5-HTP in the tumors. Linear regression analyses showed a clear correlation (r = .907) between changes in U-5-HIAA and changes in the transport rate constant for 5-HTP during treatment. CONCLUSION: PET with 11C-labeled 5-HTP demonstrated high uptake in neuroendocrine gastrointestinal tumors and thereby allowed improved visualization compared with CT. The in vivo data on regional tumor metabolism, as expressed in 11C-5-HTP uptake and transport rate, provided additional information over conventional radiologic techniques. The close correlation between the changes in 11C-5-HTP transport rate and U-HIAA during medical treatment indicates the potential of 11C-5-HTP-PET as a means to monitor therapy.

5-Hydroxytryptophan↗

Attitude towards aggression and creative functioning in patients with breast cancer.

Three projective personality tests were used to assess attitude to aggression (The Identification Test), anxiety and defenses (The Meta-Contrast Technique) and creative functioning (The Creative Functioning Test) in 70 patients with breast cancer. Discriminant analyses were applied pro primo to characterize psychologically patients with a better prognosis and patients with a poorer prognosis. A second aim was to characterize psychologically older (postmenopausal) and younger (premenopausal) women. Generally, high scores on the Identification Test indicated maladaptive attitudes towards aggression among all the patients. Patients with a poorer prognosis showed responses that in healthy subjects indicate acknowledgement of aggressive impulses, perhaps suggesting lack of "defenses" against such impulses among those patients. Another way to describe it would be that patients with a better prognosis seem to have (normally nonadaptive) "defenses" against aggressive impulses while those with poorer prognosis have not. Surprisingly, the patients with a better prognosis (but not those with a poorer prognosis) gave responses classified as depression in the Meta-Contrast Technique. Typical of premenopausal patients were responses classified as anxiety as well as reaction formation on the Identification Test. Responses classified as adaptive defenses (isolation) were seen in the Meta-Contrast Technique. A surprising finding was that many of these patients were characterized by high scores on the creativity test. These original statistically significant findings of attitudes towards aggression and creative functioning in breast cancer patients are discussed in relation to the underlying nature of aggression and creativity.

Adult↗

Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography.

Regional cerebral blood flow was measured with positron emission tomography (PET) in six healthy volunteers at rest and during experimentally induced, sustained cutaneous pain on the dorsum of the right hand or on the dorsum of the right foot. Pain was inflicted by intracutaneous injection of capsaicin, providing a mainly C-fibre nociceptive stimulus. Statistical analysis showed significant activations along the central sulcus (SI) area when comparing pain in the hand to pain in the foot. Separate comparison of both pain states to a baseline revealed different locations along the central sulcus for hand pain and foot pain. The encountered differences are consistent with what is previously known about the somatotopics of non-painful stimuli. When comparing painful stimuli to baseline, the contralateral anterior cingulate gyrus, the ipsilateral anterior insular cortex and the ipsilateral prefrontal cortex were implicated. The results are consistent with an involvement of SI in the spatial discrimination of acute cutaneous pain.

Adult↗

Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects.

OBJECTIVES: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. METHODS: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using L-[11C]DOPA, [11C]nomifensine and [11C]raclopride as tracers. RESULTS: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [11C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of L-[11C]DOPA, [11C]nomifensine and [11C]raclopride. CONCLUSION: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors.

Brain↗

Regional cerebral blood flow and oxygen metabolism during migraine with and without aura.

Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO2) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6), headache (n = 10) and after treatment with sumatriptan (n = 4). Data were analysed using an ROI-based approach from 26 different anatomically defined regions, and also an exploratory approach whereby all subjects were normalized to a stereotactic brain atlas; t-maps were constructed by depicting significant changes between states. The exploratory approach revealed a region corresponding to the primary visual cortex with significant reductions in rCBF (23.1%) and rCMRO2 (22.5%), but no change in rOER during the headache phase compared to baseline. These data suggest that cerebral ischemia was not the primary cause of the attacks in these cases.

Adult↗

Possible effects of tetrahydrobiopterin treatment in six children with autism--clinical and positron emission tomography data: a pilot study.

Six children, between 3 and 5 years of age, having infantile autism according to DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For clinical evaluation, the Parental Satisfaction Survey (PASS) was used every fourth week and the Griffiths Developmental Scales were used before starting and 3 months after completing the treatment. During the treatment period, all parents reported improvements in the child's social functioning-mainly eye contact and desire to interact-and in the number of words or sounds which the child used. Small positive changes were noted on the Griffiths Developmental Scales between the two testing occasions. R-BH4 levels in CSF increased significantly after treatment. The positron emission tomography (PET) study showed that the high value of dopamine D2 receptor binding in the caudate and putamen decreased by about 10% towards the normal level after treatment with R-BH4. The observations in this open study indicate that the drug might be useful for a subgroup of children with autism, but there is a need for a larger double-blind study with a longer treatment period.

Antioxidants↗

Early mental changes in patients with astrocytomas with special reference to anxiety and epilepsy.

This study of 47 patients with low- and high-grade gliomas retrospectively focuses on the patients' history with regard to affective and cognitive disturbances as well as to the presence of epileptic manifestations. Early emotional changes with a sudden onset were common in both patient groups, especially panic-like anxiety. It is suggested that patients with a high-grade glioma may present with affective disturbances with a sudden onset, while such disturbances in patients with low-grade gliomas could be of epileptiform origin. It is also suggested that the biochemical bases of anxiety and epilepsy in glioma patients could be analyzed to understand underlying biopsychological mechanisms of malignant brain tumors.

Adult↗