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Biomedical subjects

C Muhr

Publications and source records attributed to C Muhr.

At least 19 recordsLinked to original sources
PubMed1992

MRI of pituitary macroadenomas with reference to hormonal activity.

In 115 patients with pituitary macroadenomas, the findings on mid-field MRI were correlated with the hormonal activity of the tumours. Adenomas secreting growth hormone (GH), prolactin (PRL) and clinically nonsecretory adenomas were studied. Tumour size, invasiveness and signal intensity patterns were recorded. Relaxation times and ratios of signal intensity and proton density (relative to the corpus callosum) were analysed in areas of apparently solid tissue in a subgroup of 59 previously untreated patients. Invasiveness was more common in PRL- and GH-secreting adenomas than in the nonsecreting ones. Diffuse invasion of the base of the skull was most common in prolactinomas, and associated with a lower frequency of suprasellar tumour extension. In prolactinomas, a correlation was found between the maximum serum PRL level and tumour size. Haemorrhagic, cystic or necrotic areas were less common in GH-secreting tumours than in the other types. Haemorrhage was more common in prolactinomas than in nonsecreting tumours. MR parameters were similar in prolactinomas and nonsecreting adenomas, but indicated a smaller amount of water in GH-secreting tumours.

Adenoma↗
PubMed1992

Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L-deprenyl.

Seven patients with clinically nonsecreting pituitary adenoma and 5 patients with meningioma were examined with positron emission tomography using [11C]-LL-deprenyl and [11C]-LL-methionine. The dynamics of the uptake of [11C]-L-deprenyl in the pituitary adenomas demonstrated a rapid and high uptake immediately after the injection, and, later, an almost constant level was observed that was equal to or higher than that observed in normal brain tissue. In the meningiomas, however, the initially high uptake was followed by a marked decrease with time, reaching a level that was approximately half that observed in brain tissue. The study demonstrated high binding of [11C]-L-deprenyl to monoamine oxidase B in pituitary adenomas, whereas the binding in meningiomas was very low. This fact can be used in the differential diagnosis of pituitary adenoma and parasellar meningioma. Operative samples from 10 patients with meningioma and from 5 patients with pituitary adenoma were analyzed biochemically for activity of monoamine oxidase B, using [14C]-phenyl-ethylamine as substrate. The nonsecreting pituitary adenomas demonstrated high enzyme activity, the secreting adenomas about one-tenth of that of the nonsecreting, and the meningiomas one-thirtieth of that of nonsecreting adenomas.

Adenoma↗
PubMed1991

Effects of the PAF-analog and -antagonist CV-6209 on cultured human glioma cell lines.

Cell lines of human glioma (U-343 MGa and U-251 MG) and human glia (U-533 CG) origin were cultured as monolayers and exposed to CV-6209, an alkyl-phospholipid analog and antagonist of platelet activating factor. This drug had very potent antiproliferative effects on the studied human glioma cell lines; IC50 was 0.9 microM after 48 h treatment and 0.2 microM after 2 weeks treatment. At these doses no growth inhibitory effect was noted on the normal glia cells. The effects on the glioma cells were reversible in the dose intervals, where cell proliferation, 3H-thymidine and 14C-methionine uptakes were greatly inhibited. The simultaneous administration of platelet activating factor [(R)PAF] did not influence the antiproliferative effects of CV-6209 on the cells cultured as monolayers. The structurally similar analog CV-3988 also had antiproliferative effects, although at 10 times higher concentration than CV-6209. Two other, structurally unrelated, PAF-antagonists (WEB-2086 and TCV-309) gave effects only at very high concentrations. The U-343 MGa cell line was also exposed to CV-6209 when growing as multicellular spheroids. The studies on the spheroid cultures also demonstrated good antitumoral effects with decreases of both the volume growth and the thymidine uptake. The simultaneous administration of (R)PAF reversed the inhibitory effect of CV-6209 on thymidine incorporation. This study demonstrates a strong antitumoral effect at low concentrations of CV-6209. The antiproliferative effects were probably primarily related to the ether-lipid structure and not to the PAF-antagonistic properties. The good antitumoral effect of CV-6209 on both monolayer and spheroid cultures and the possible PAF-antagonistic properties are discussed.

Cell Division↗
PubMed1991

In situ hybridization histochemistry of mRNAs for hormones and chromogranins in normal pituitary tissue and pituitary adenoma.

In situ hybridization histochemistry was employed to detect mRNAs of pituitary hormones and chromogranins in normal pituitary gland and pituitary adenomas. Oligonucleotide probes specific to the mRNAs for prolactin, growth hormone, proopiomelanocortin, the alpha- and beta-subunits of the glycoprotein hormones and chromogranins A and B were used in the hybridization experiments. The oligonucleotides of 27 to 51 bases were labelled radioactively with dATP[alpha-35S] at the 3'-end using terminal deoxynucleotidyl transferase. Positive hybridization reactions were visualized by autoradiography in the normal pituitary gland with all of the probes. The clinically diagnosed pituitary adenomas (prolactinoma, acromegaly, Cushing's disease, FSH-secreting tumour) showed positive hybridization with the corresponding oligonucleotide probes. In some cases positive hybridization was also obtained with other probes, suggesting multihormone-producing character of the tumour cells. A microprolactinoma was found in a pituitary gland obtained from a patient without any known pituitary disorders. Examination of mRNAs for chromogranin A and B revealed that the normal pituitary gland contains a larger number of cells expressing chromogranin B and a lower number expressing chromogranin A and, moreover, the microprolactinoma lacked the expression of mRNA for chromogranin A but expressed that of chromogranin B.

Adenoma↗
PubMed1991

Application of (methyl-11C)-methionine in the multicellular spheroid system.

Human glioma (U-343 MGa) and human colon carcinoma (HT-29) cell lines were cultured as multicellular spheroids, and the accumulations of the L- and D-enantiomers of 11C-methionine were investigated. The accumulation of radioactivity in the spheroids was expressed as relative counts, by dividing the radioactivity measured in the spheroid with the radioactivity of the same volume of the incubation medium. The experiments were verified using 14C-labeled L- and D-methionine. The influence of spheroid volume, specific activity, incubation time, washing time, and the environmental temperatures were investigated. The spheroid model was used to determine the effect of the lipoxygenase inhibitors BW A4C and AA-861, the ether-phospholipid type PAF-antagonist CV-6209 and the protein synthesis inhibitor cycloheximide on methionine uptake. The results showed that 11C-L-methionine can be applied in the study of drug effects on multicellular tumor cell aggregates.

Benzeneacetamides↗
PubMed1991

PET as a tool in the clinical evaluation of pituitary adenomas.

Positron emission tomography (PET) was used in over 400 examinations in patients with pituitary adenoma. It was demonstrated that PET with carbon-11-methionine can give valuable complementary information in the diagnosis of this tumor due to PET's ability to adequately depict viable tumor tissue in contrast to fibrosis, cysts and necrosis. Furthermore, PET with dopamine D2 receptor ligands can characterize the degree of receptor binding and thus give information as to the prerequisites for dopamine agonist treatment. Most important is the very high sensitivity given by PET with carbon-11-methionine in the evaluation of treatment effects. It is concluded that when properly used PET can be fully justified in the clinical handling of patients with pituitary adenomas and other intracranial tumors.

Adenoma↗
PubMed1991

Comparison of MR imaging and CT in pituitary macroadenomas.

The findings on mid-field MR imaging and CT were compared retrospectively in 65 patients with pituitary macroadenomas. The evaluation comprised tumour extension and delineation, invasiveness, relationship to adjacent structures, and internal tumoral changes. MR was superior to CT except in the demonstration of bone changes and tumour calcification. The superiority of MR was most pronounced regarding cavernous sinus invasion, tumour relationship to the carotid arteries and optic chiasm, and tumour haemorrhage. Extensive bone changes were visualized with both methods; erosions were often seen only with CT. It is concluded that MR is the preferable method for evaluation of pituitary macroadenomas. CT is useful as a supplementary modality when detailed information on bone anatomy is required, particularly if a transsphenoidal surgical approach is contemplated.

Adenoma↗
PubMed1990

Effects of prostaglandin and leukotriene inhibitors on the growth of human glioma spheroids.

Established cell-lines of human glioma origin were cultured as multicellular spheroids or as monolayers. Volume growth and 3H-thymidine labelling were analysed for the spheroids after continuous exposure to drugs interfering with the release of arachidonic acid and the production of prostaglandins and leukotrienes. Comparative measurements were made on monolayer cultures. The cyclo-oxygenase inhibitor indomethacin enhanced growth at intermediate concentrations (0.5-5.0 micrograms/ml) but reduced growth at 50 micrograms/ml. The dual cyclo-oxygenase and lipoxygenase inhibitor ketoprofen had a significant inhibitory effect on growth and cell proliferation of spheroids at high concentration (50 micrograms/ml). The weak lipoxygenase inhibitor NDGA (quinone-form) decreased growth whereas the strong lipoxygenase inhibitor NDGA (hydroquinone-form) did not reduce growth rate but significantly decreased cell proliferation. Quinacrine reduced the spheroid growth rate although dexamethasone had no effects. Thus, inhibitors of the arachidonic acid cascade had growth inhibitory effects in the spheroid tumour model as well as in cells cultured as monolayers.

Arachidonic Acids↗
PubMed1990

Effects of the 5-lipoxygenase inhibitors AA-863 and U-60,257 on human glioma cell lines.

The effects of two specific 5-lipoxygenase inhibitors AA-863 and U-60,257 (piriprost) on the growth of two human glioma cell lines, U-343 MGa and U-251 MG were investigated. Both monolayer cultured cells and spheroids were studied. The results of the monolayer studies showed potent and dose dependent inhibitory effects on the proliferation of glioma cells (IC50/one week treatment/of AA-863: 9.0 microM, IC50 of U-60,257: 40.0 microM). The experiments made on the tumor spheroids suggested an inhibitory effect on proliferation and volume growth already at lower doses (AA-863: 0.4-2.0 microM, U-60,257: 1.0-5.0 microM), a dose range where effects were not found in monolayers. At higher doses (AA-863: 10.0-30.0 microM, U-60,257: 30.0-90.0 microM) the experiments with spheroids failed to demonstrate a further inhibitory effect on spheroid volume, probably attributed to phenomena such as swelling of cells, dissociation of spheroid structure and development of necrosis. The clearly dose dependent inhibitory effect on the proliferation of human glioma cells in monolayer culture and the inhibitory effects on spheroid growth with these specific inhibitors indicate a role for lipoxygenase products in the growth of gliomas.

Arachidonate Lipoxygenases↗
PubMed1989

[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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗