Does alpha-interferon in conjunction with radiotherapy increase the risk of complications in the central nervous system?
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Adult↗
Biomedical subjects
C Muhr
Publications and source records attributed to C Muhr.
[PET--new ways inside the body].
Using positron-emitting short-lived radionuclide tracers, a wide range of substances can now be labelled without their biological properties being affected. Positron emission tomography (PET) enables the distribution and metabolism of the labelled substance to be studied in different organs. By providing quantitative, locational, functional and biochemical information difficult to obtain by other means, PET opens up new possibilities, both diagnostic, pathophysiological and therapeutic, in a broad spectrum of medical practice. The development of the technique is described, with particular reference to its use at Uppsala.
Abdominal Neoplasms↗
Malignant prolactinoma with multiple intracranial metastases studied with positron emission tomography.
A rare case of a patient with multiple intracranial metastases from a prolactin-secreting pituitary neoplasm is described. At the age of 14 years, the patient had been operated on for a sellar tumor; he presented 12 years later with severe headache, at which time computed tomographic and magnetic resonance imaging scans revealed multiple intracranial metastases. Histopathology examination showed pituitary neoplastic cells with positive immunostaining for prolactin. The patient was investigated with positron emission tomography (PET) and dopamine D2-receptor binding, and the amino acid metabolism of the tumor was characterized in vivo. High dopamine D2-receptor binding and high amino acid metabolism were found in the tumor. The patient was subsequently treated with bromocriptine injections that resulted in a decrease in serum prolactin levels, decreased dopamine D2-receptor binding, reduced amino acid metabolism, and a reduction in tumor volume. This case demonstrates a beneficial effect of bromocriptine treatment in a patient with prolactinoma with multiple intracranial metastases. It also illustrates the great potential of PET in the in vivo characterization of the D2-binding and the high sensitivity of 11C-labeled L-methionine in the follow-up of treatment in patients with pituitary adenomas.
Adenoma↗
The normal pituitary examined with positron emission tomography and (methyl-11C)-L-methionine and (methyl-11C)-D-methionine.
Four patients with radiologically normal pituitary gland were examined with positron emission tomography after the administration of (methyl-11C)-L-methionine. On a following day the examination was repeated with (methyl-11C)-D-methionine. The accumulation rate of L-methionine in the pituitary was measured, giving a value that was about twice that of normal brain tissue. The accumulation rate of D-methionine in the pituitary was almost a factor of 10 lower than that of L-methionine. In the normal brain tissue that ratio was 2.3. The study clearly indicates that the methionine uptake in the pituitary is stereospecific. 11C-D-methionine is freely distributed in the tissue without entrapment, whereas 11C-L-methionine is irreversibly bound. It is concluded that PET with 11C-L-methionine can be used to study amino acid utilization in the pituitary.
Adult↗
Transsphenoidal therapeutic puncture of a cystic pituitary adenoma.
Transsphenoidal diagnostic puncture of skull base tumours has been a routine procedure in Uppsala for a decade. Bromocriptine is the treatment of choice for patients with prolactin secreting pituitary adenomas. Here we report on a patient with a pituitary adenoma who instead developed an increase in tumour size after bromocriptine treatment. Magnetic resonance imaging showed the tumor to be cystic. A transsphenoidal puncture was used therapeutically instead of surgery with excellent result.
Adenoma↗
Kinetics of four 11C-labelled enkephalin peptides in the brain, pituitary and plasma of rhesus monkeys.
The kinetics of four 11C-labelled enkephalin peptides: Tyr-Gly-Gly-Phe-Met (Met-enkephalin), Tyr-D-Met-Gly-Phe-Pro-NH2 [D-Met2,Pro5)-enkephalinamide), Tyr-D-Ala-Gly-Phe-Met-NH2 (DALA) and Tyr-D-Ala-D-Ala-Phe-Met-NH2 (TAAFM) all labelled at the methyl group of methionine was studied in the Rhesus monkey. After intravenous administration, the regional kinetics in the head, lungs, liver and kidneys were followed by means of positron emission tomography (PET). The total radioactivity in blood and urine was measured and the composition of 11C-labelled peptide fragments in plasma in vivo and in vitro was analysed by liquid chromatography. With PET, an increased radioactivity was observed in the brain and pituitary over the 60-90 min investigation period after i.v. injection of the peptides. The highest radioactivities were noted for Met-enkephalin, followed by DALA and D-Met2, Pro5-enkephalinamide, while very low radioactivities were found for TAAFM. The uptake of Met-enkephalin- and DALA-derived radioactivity was of the same order as has previously been shown for morphine in the brain and considerably higher than that of D-Met2,Pro5-enkephalinamide and TAAFM, respectively. A large fraction of the brain radioactivity derived from Met-enkephalin and DALA probably emanated from [11C]methionine as indicated by plasma and urine analysis. Met-Enkephalin was rapidly eliminated from plasma in vitro with an half-life of less than two minutes, whereas DALA was stable suggesting clearance by other tissues than plasma. In conclusion, both Met-enkephalin and DALA, were rapidly hydrolyzed in vivo to [11C]methionine. [11C]Methionine was probably taken up in the brain, as the radioactivity increased with time in different brain regions as measured with PET.D-Met2,Pro5-Enkephalinamide and TAAFM were virtually stable in vivo and at least part of the radioactivity observed in the brain may have represented the intact peptide.
Animals↗
Magnetic resonance imaging of tumours of the sellar region. Evaluation of treatment with bromocriptine retard.
Magnetic resonance imaging (MRI) with a superconductive 0.5 T magnet has been used in 10 patients with pituitary adenomas to evaluate the effect of bromocriptine treatment. Seven patients had prolactinomas, one a growth hormone (GH) producing adenoma and two patients null cell adenomas with slight hyperprolactinaemia. A single dose of 50 mg bromocriptine was given intramuscularly in a slow release preparation, followed after 6 weeks by 5 mg/day orally. Significant reduction of serum prolactin was noticed in all patients. Visual field defects disappeared rapidly. In all prolactinoma patients and in the patient with the GH producing adenoma MRI showed a decrease in tumour size. In 5 of these 8 patients MR signal analysis, aided by the use of a subtraction technique, clearly visualized the development of large intratumour cysts. In one further patient with a null cell adenoma there was also a rapid development of an intratumour cyst and an increase in tumour size. This patient was treated with transsphenoidal needle aspiration. In all tumour cases an increase in intensity quotients based on T1 and T2 relaxation times was calculated.
Adenoma↗
In vivo measurement of dopamine receptors in pituitary adenomas using positron emission tomography.
Patients with pituitary adenomas were examined with positron emission tomography (PET) with the administration of the 11C-labelled dopamine-D2 antagonists N-methylspiperone and raclopride. The studies were repeated after protection of the D2-receptors with Haloperidol to enable a separation of specific and unspecific receptor binding. The receptor binding was evaluated by visual inspection and with the application of a kinetic model. The results showed marked specific dopamine-D2 receptor binding in the prolactinomas and minimal or no such binding in the hormonally inactive adenomas. The two tracers 11C-raclopride and 11C-N-methylspiperone showed qualitatively the same result although raclopride resulted in a higher tumor to normal brain ratio. In conclusion, PET is a valuable complement to other radiologic techniques like computed tomography and magnetic resonance imaging in the evaluation of pituitary adenomas. An assessment of the dopamine-D2 receptors in the adenomas has a direct influence on the choice of treatment because adenomas with high amounts of receptors are in most cases effectively treated with dopamine agonists like bromocriptine.
Adenoma↗
Amino acid metabolism in pituitary adenomas.
Patients with pituitary adenomas were examined with positron emission tomography with the administration of 11C-labelled methionine. In a few patients comparative studies using the two stereo-isomers L- and D-methionine were also performed. The results showed a rapid distribution of D-methionine within the tumor tissue without signs of irreversible trapping of the tracer. L-methionine on the other hand was rapidly irreversibly trapped indicating the metabolic fate. It is concluded that 11C-L-methionine can be used to quantify amino acid metabolism in the tumors. The amino acid metabolism was evaluated in a group of adenomas before and after treatment with bromocriptine. The results indicate a marked reduction of the amino acid metabolism in prolactinomas amounting to 60%. These tumors at a later time responded with tumor shrinkage. Hormonally inactive tumors showed no effect of treatment.
Adenoma↗
Prolactinomas in men: clinical characteristics and the effect of bromocriptine treatment.
Thirty-seven men with prolactin (PRL) producing pituitary adenomas were studied to elucidate if patient's delay might cause the predominance of large tumours in men as compared to women in whom microadenomas predominate. We found two clinical subgroups; one presented with short duration of symptoms, dominated by local signs from the growth of notably large tumours, the other exhibited a long history of disease with hypogonadism as the dominating symptom. There was a correlation between tumour size and PRL levels. The age at the time of diagnosis showed no correlation to duration of symptoms, size of adenoma or PRL levels. Four patients with small adenomas, moderate hyperprolactinemia and short duration of symptoms showed signs of hypergonadotropic hypogonadism. Surgery or irradiation, performed in 14 patients, did not normalize PRL levels. Bromocriptine was equally beneficial in the two clinical subgroups, improving clinical symptoms and normalizing PRL levels in all but three patients. The study shows that the predominance of large tumours in men does not depend on patient's or doctor's delay, but on a high frequency of presumably rapidly growing PRL producing tumours. In the majority of patients, these tumours do not give signs of hypogonadism before the tumour is revealed by local signs of tumour growth.
Adult↗
Screening for multiple endocrine neoplasia syndrome (type 1) in patients with primary hyperparathyroidism.
In 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma-(MEN)-syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG-alpha and -beta). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN-1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo- or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG-alpha and -beta levels were within the normal range in all patients but two. We conclude that the incidence of MEN-1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.
Adult↗
A parallel study of the roentgen anatomy of the sella turcica and the histopathology of the pituitary gland in 205 autopsy specimens.
To further elucidate to what extent minor sellar roentgenological changes imply the presence of a microadenoma or other histopathological findings in the pituitary gland, an autopsy series of 205 cases was investigated. Plain sellar films and multidirectional tomograms in frontal and lateral projections were obtained and the pituitary gland was histopathologically examined after being serial sectioned. Sloping of the sellar floor amounting to 2-14 degrees was found in 39 cases and minor cortical changes and configuration variations (locally thinner cortical layer, erosion and bulging) were seen in 23 cases. Histopathology revealed a solitary tumour in the anterior lobe in three cases and focal nodular hyperplasia in a fourth case. The diameter of these nonencapsulated 'adenomas' varied between 3 and 5 mm. Small cysts were a fairly common finding and fibrous tissue was present in about every second gland. No correlation was found between the roentgenological changes of the sella and histopathological findings in the gland. It was concluded that the type of roentgenological sellar findings described should be considered as normal variations without pathological significance when diagnosing a pituitary microadenoma.
Adenoma↗
Weekly headache periodicity and the effect of weather changes on headache.
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Adult↗
Pituitary adenomas: computed tomography and clinical evaluation in a follow-up after surgical treatment.
A study of the recurrence rate in 41 patients operated and postoperatively treated with irradiation for a pituitary adenoma was performed 10-15 years after operation. 15 of the 41 patients are now deceased among whom 1 had a known recurrence. 25 out of the now 26 living patients were investigated with a clinical examination, perimetry, computed tomography (CT), roentgen examination of the sella turcica and an endocrine evaluation. The outstanding capability of the CT to visualize pituitary adenoma recurrences was clearly demonstrated as this technique revealed recurrences in 6 patients, only 2 of which had progressive visual field defects and none progressive changes on plain sellar films.
Adenoma↗
Follow-up study with computerized tomography and clinical evaluation 5 to 10 years after surgery for pituitary adenoma.
This study was based on 24 consecutive patients operated on for pituitary adenoma with suprasellar extension, and treated postoperatively with radiotherapy. The follow-up period was 5 to 10 years. A clinical examination, endocrine evaluation, perimetry, computerized tomography (CT) and sellar roentgenography were performed in 19 of 20 surviving patients. The CT scans revealed four recurrences, while perimetry only showed an increased visual field defect in one patient. Plain sellar films were of no value for diagnosis of recurrence. Prolactin determinations seemed to have a limited value in recurrence diagnosis, but very high levels spoke in favor of a recurrence. Thus, CT was found to be the superior method of diagnosing recurrences. It is proposed that CT be used regularly in the follow-up study of patients operated on for a pituitary adenoma.
Adenoma↗
Weekly periodicity of headache and the effect of changes in weather on headache.
The effect of changes in weather on headache was investigated in two separate studies in Uppsala. In a pilot study 60 healthy persons (all medical staff) reported their headache during a period of 2 months. Later 53 patients with migraine and 20 with tension headache registered their headache during 4 weeks. Several climate factors were recorded during the observation periods. Both studies showed a significant weekly periodicity of headache. In patients with migraine the headache frequency was lowest on Sunday-Monday and highest on Thursday and on Saturday. In patients with tension headache the highest frequency was noted on Thursday-Friday and lowest frequency on Sunday-Tuesday. The pilot study showed that personnel off work had significantly more headache when bad weather occurred. There was a tendency for headache the day before windy weather. In the 53 migraine patients there was also a correlation between some climate factors and headache frequency. In this group the deviation from the expected headache frequency (actual headache frequency minus that of observed weekly periodicity) correlated significantly to the air-pressure and air-temperature measured 1-3 days later.
Adult↗
Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone.
Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.
Adenoma↗
Amino acid distribution and metabolism in pituitary adenomas using positron emission tomography with D-[11C]methionine and L-[11C]methionine.
Four patients with hormonally inactive pituitary adenomas were examined with positron emission tomography (PET) after injection, during different examinations, of L-[methyl-11C]methionine and D-[methyl-11C]methionine, respectively. After the rapid distribution phase, the enantiomer L-[11C]methionine, which is metabolically active, showed a considerable continuous irreversible trapping attributed to amino acid metabolism. The stereoisomer D-[11C]methionine, which does not participate in protein synthesis, showed a rapid distribution within the whole adenoma tissue, with a distribution space on the order of 100%. A minimal irreversible trapping was observed which could be explained by technical factors. It is concluded that PET using the two enantiomers allows a separation of passive distribution and metabolism, and that L-[11C]methionine can be used for in vivo quantitative studies of amino acid metabolism of pituitary adenomas.
Adenoma↗