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Biomedical subjects

B Karlsson

Publications and source records attributed to B Karlsson.

At least 91 records · Page 5Linked to original sources

Combined embolization and gamma knife radiosurgery for cerebral arteriovenous malformations.

In a study of 46 patients with cerebral arteriovenous malformations (AVMs) the value of combining embolization and gamma knife radiosurgery was assessed. In 35 patients with large grade III to V AVMs (Spetzler-Martin system) staged combined treatment was planned. In 11 patients, radiosurgery complemented embolization for a residual AVM. The number of embolization sessions ranged from 1 to 7 (median 2). Twenty-six patients needed multiple embolization sessions. In 28 patients the grade of AVMs decreased as a result of embolization. In 16 patients collateral feeding vessels developed after embolization which made delineation of the residual nidus difficult. The time lag between the last embolization and radiosurgery ranged from 1 to 24 months (median 4). Nineteen of 35 large grade III to V AVMs were possible to treat by radiosurgery following embolization. In the 46 patients complications occurred in 9 from embolization and in 2 from radiosurgery. Two patients had transient and 9 had permanent neurologic deficits. It is concluded that embolization facilitates radiosurgery for some large AVMs and therefore this combined treatment has a role in the management of AVMs.

Adolescent↗

Target delineation in radiosurgery for cerebral arteriovenous malformations. Assessment of the value of stereotaxic MR imaging and MR angiography.

A study of 6 selected arteriovenous malformation (AVM) patients was performed to investigate the feasibility of delineating an AVM on MR images and to compare the AVM volume outlined on different images. Conventional stereotaxic angiograms, stereotaxic MR images and MR angiograms using several different pulse sequences were obtained prior to radiosurgery. Treatment plans were made from the conventional stereotaxic angiograms. These plans were then transferred to a separate dose planning computer which displayed the MR images with the superimposed isodose lines. The radiated volumes of AVM and brain tissue were measured from these MR images. Last, an assessment was made of the radiation volume needed for an appropriate treatment of the AVM if the treatment plan was made from the MR images rather than from the conventional stereotaxic angiogram. It was possible to delineate medium and large size AVM nidi on stereotaxic MR images based on an integration of information obtained from various pulse sequences. The estimated volumes of the AVM nidi were found to be larger on the conventional stereotaxic angiograms than on the stereotaxic MR images. Consequently, a dose plan based on a conventional stereotaxic angiogram would result in a higher integral dose to the brain with the same target dose. By using reliable MR information it is expected that the volume of brain exposed to radiation could be decreased and the adverse effects of stereotactic radiosurgery for AVM thereby minimized.

Adult↗

The use of endovaginal ultrasound to diagnose invasion of endometrial carcinoma.

Endovaginal ultrasound was used in 30 women to characterize endometrial carcinoma with respect to myometrial invasion according to FIGO recommendations for surgical staging of endometrial cancer. The ultrasound data were correlated to macroscopic findings of the uterine specimen and to histopathology. Using endovaginal ultrasound, the sensitivity of detecting myometrial invasion of > 50% was 15/19 or 79%. However, the positive predictive value was 100%, in all cases when ultrasound suggested myometrial invasion of > 50%. This was confirmed on histopathological examination of the tumor specimen. Cervical tumor extension was correctly diagnosed in all six women in which it was present. Endovaginal ultrasound seems to be a reliable method of assessing tumor invasion and engagement of the cervix. This non-invasive method could be included as an important tool in the establishment of individualized treatment programs in women with endometrial carcinoma.

Journal Article↗

Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal antibodies in nude mice.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

Animals↗

Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice.

Two immunotoxins were constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A (PE) or a modified form, NlysPE40, that lacks the cell binding domain of PE. Monoclonal antibody C242 recognizes a specific sialylated carbohydrate epitope on a high molecular weight membrane glycoprotein present on cells of human colon, pancreatic, and cervical cancers. C242-PE and C242-NlysPE40 were very cytotoxic for cells expressing this antigen with 50% inhibition of protein synthesis occurring on Colo205 cells at 0.2 ng/ml (0.9 pM) for C242-PE and 6.0 ng/ml (31 pM) for C242-NlysPE40. The two immunotoxins also exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice. The specificity and potency of these two C242 immunotoxins warrant their further development for the treatment of cancer.

ADP Ribose Transferases↗

Gamma knife surgery for cerebral metastasis.

Twenty-six cerebral metastatic tumours treated with the Gamma knife employing a large single dose were followed by repeated clinical and CT examinations. In most cases Gamma knife surgery was the only treatment. The follow up time has been longer than 6 months with a median follow up of 9 months. In all but one of the cases a remarkable progressive shrinkage of the tumour started 2-4 months after the therapy. The therapeutic results indicate that radiosurgery used even as the only form of treatment is the best treatment alternative for cerebral metastasis presently available.

Aged↗

Monoaminergic dysfunction in Sjögren-Larsson syndrome.

The anteroposterior distribution of monoamine and monoamine metabolite concentrations was determined in subcortical brain nuclei of two cases of Sjögren-Larsson syndrome (SLS) and was compared to two control cases. The brains were divided into halves and sectioned coronally. For biochemical analyses, caudate nucleus, putamen, globus pallidus, substantia nigra, nucleus accumbens, amygdala, and hippocampus were dissected macroscopically. Monoamine and its metabolites were determined by reverse-phase liquid chromatography with electrochemical detection. The other hemisphere was studied neuropathologically. The SLS cases revealed cell loss in substantia nigra and putamen and a widespread white-matter destruction. Biochemically, most pronounced alterations were seen in the dopamine system in putamen with severely reduced concentrations of dopamine (DA; 14% of control values) and the catabolic metabolites 3-methoxytyramine (3-MT; 9% of control values) and homovanillic acid (HVA; 20% of control values). In substantia nigra and the other striatal regions studied, a general decrease of 3-MT and HVA concentrations was observed in the SLS subjects compared to the controls, although the decrease was less pronounced than in putamen. Generally, somewhat reduced noradrenaline and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were seen in the SLS cases, whereas serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were increased compared to the controls in most regions studied. These data suggest a specific monoaminergic dysfunction in patients with SLS. The severe decline in the dopaminergic system in putamen suggests that supplementation of dopamine agonists may ameliorate the symptoms of SLS patients.

Biogenic Monoamines↗

Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.

Diagnostic curettage has for many years been the method of choice to diagnose endometrial cancer in women with postmenopausal bleeding. The costs for curettage performed today are huge, and approximately only 10% in this group of women will be diagnosed with endometrial cancer. Thus less expansive techniques to obtain endometrial samples have been evaluated, but all of them are invasive. The value of endovaginal ultrasonography for identifying endometrial abnormality in this group of women has not been evaluated until now. This study used endometrial thickness as measured by endovaginal ultrasonography as an indicator of endometrial abnormality. It was demonstrated in 205 women with postmenopausal bleeding that if the endometrium was less than 9 mm thick, no endometrial cancer was found at curettage. The mean endometrial thickness in those women with endometrial cancer was 18.2 +/- 6.2 mm as compared with 3.4 +/- 1.2 mm in those women with atrophic endometrium. If the cutoff limit for endometrial abnormality was 5 mm, the positive predictive value for identifying endometrial abnormality was 87.3%. If this limit had been used in this study, 70% of the curettage procedures could have been avoided.

Endometrium↗

Mutagenicity testing of condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures.

Condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures were investigated for their potential to produce genetic damage in the tester strains TA98, TA100, TA1535 and TA1537 of Salmonella typhimurium and in the mouse bone marrow micronucleus assay. Both smoke condensates contained several chlorinated hydrocarbons among which tetrachloroethylene, hexachloroethane, hexachlorobutadiene and hexachlorobenzene were identified by GC/MS. Condensate of smoke from titanium dioxide/hexachloroethane showed a dose-related positive response in the Salmonella assay with strains TA98 and TA100 in the absence of metabolic activation from rat liver S9 fraction. Both smoke condensates were negative in the micronucleus assay but produced a small but significant depression of erythropoietic activity. The results indicate that smoke condensate from titanium dioxide/hexachloroethane mixtures contains unidentified compound(s) that may be considered mutagenic in the Salmonella assay.

Animals↗

Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction.

BACKGROUND AND PURPOSE: We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction. METHODS: We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein). RESULTS: We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients. CONCLUSIONS: Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients.

Adult↗

Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.

Adenocarcinoma↗

A strategy for ranking environmentally occurring chemicals. Part VI. QSARs for the mutagenic effects of halogenated aliphatics.

A strategy for the systematic analysis and priority ranking of environmental chemicals has been applied to a class of 58 halogenated aliphatic hydrocarbons. A training set of ten compounds representing this class, was selected by statistical design. The training set compounds were then subjected to biological testing in the Salmonella typhimurium reverse mutation assay (Ames test). The measured biological data, recorded as dose-response curves, were analyzed to determine the mutagenic potency (slope of the initial portion) and the mutagen dose (MD 50) required to increase the number of revertants above the background by 50%. For each compound, four mutagenic potency estimates and four MD 50 values were determined, all originating from the tester strains TA 100 and TA 1535 with and without metabolic activation. The obtained responses were analyzed with multivariate techniques to give QSAR models relating the mutagenic potency data to the physico-chemical properties of the compounds. Finally, the derived QSARs were used to predict the mutagenic potencies and the MD 50S for the non-tested compounds in the class.

Chemical Phenomena↗

On the use of diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide), as adjunct antidotes in the treatment of organophosphorus intoxication in the guinea-pig.

Diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide) have been used as adjunct antidotes to pyridostigmine and atropine against the organophosphate, soman, in the guinea-pig. Both added significant protection to the pyridostigmine/atropine treatment. Animals pretreated with diazepam, 60 min before soman, were "better" protected than animals given an equimolar dose of pro-diazepam therapeutically 1 min after soman. A pretreatment with diazepam for three days further increased the protection. A therapeutic dose of pro-diazepam, 1 min after soman, gave no further protection, to the three day diazepam pretreatment. The serum concentrations of diazepam (given i.p.) and desmethyldiazepam (given i.m.) were determined by GLC after diazepam (i.p.) and pro-diazepam (i.m.) were given. The protection, relative to the control, provided by the diazepam pretreatment (60 min before and for three days before soman) correlated linearly, r = 0.9898, with the serum values of diazepam achieved at these times. Our data suggest that diazepam as adjunct to pyridostigmine and atropine administered as pretreatment gives a "safer" protection, than an equimolar dose of pro-diazepam given therapeutically.

Animals↗

Pancreastatin inhibits insulin secretion and exocrine pancreatic secretion in the pig.

Pancreastatin is a 49 amino acid peptide that occurs in pancreatic endocrine cells. Porcine pancreastatin has previously been shown to inhibit insulin secretion in vitro in the rat and in vivo in mice and dogs. However, the effects of this novel peptide in the porcine pancreas, i.e., in its species of origin, have not yet been established. Therefore, we have investigated the effects of porcine pancreastatin on the secretion of insulin and pancreatic juice (volume, protein and trypsin) from the porcine pancreas in vivo. The peptide was infused for 10 min at 74 pmol/min into the superior pancreatic artery either alone (blood glucose level 4.3 +/- 0.5 mM) or during an ongoing intravenous infusion of glucose (blood glucose level 11.0 +/- 2.2 mM). Blood was sampled from the portal vein and pancreatic juice was sampled from the cannulated pancreatic duct. We found that pancreastatin reduced the portal venous concentration of insulin, both during normoglycemia (from 28 +/- 3 to 12 +/- 4 microU/ml; p less than 0.001) and during hyperglycemia (from 53 +/- 6 to 17 +/- 5 microU/ml; p less than 0.001). Likewise, pancreastatin reduced the secretion of both protein (from 177 +/- 42 to 92 +/- 30 mg/h; p less than 0.05) and trypsin (from 93 +/- 19 to 57 +/- 17 U/h; p less than 0.05) in pancreatic juice without significantly altering the secreted volume. In conclusion, in the porcine pancreas in vivo, porcine pancreastatin (a) inhibits insulin secretion, and (b) inhibits the secretion of protein and trypsin to the pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Autonomic control of the diurnal variation in arterial blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats.

The relative influences of sympathetic and parasympathetic neural modulation on mean arterial pressure (MAP) and heart rate (HR), and their respective variabilities, were studied in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and HR in unrestrained rats. In addition, the autonomic nervous control of MAP and HR was studied in ageing SHR and WKY. Both WKY and SHR showed diurnal rhythms with regard to MAP and HR. The MAP variability was higher in SHR than in WKY during both daytime (inactive) and night-time (active), and did not change in response to either beta 1-adrenoceptor- or cholinergic blockade. Structural vascular changes, with a resultant increase in reactivity, may explain the elevated MAP variability in SHR. HR variability was clearly reduced in SHR; this was not influenced by vagal blockade, whereas HR variability was significantly reduced in WKY. This pattern is suggested to be due to a reduced tonic vagal discharge in SHR, as part of a persistent, mild defence reaction. The initial reduction in vagal activity will in turn eliminate vagally mediated tachycardias. Furthermore, administration beta 1-blockade to SHR of different ages caused a greater fall in MAP and HR than in WKY, indicating an increased dependence upon the sympathetic nervous system in SHR with age.

Animals↗

Sympathetic and parasympathetic influence on blood pressure and heart rate variability in Wistar-Kyoto and spontaneously hypertensive rats.

The relative influence of sympathetic and parasympathetic nervous control of heart rate and heart rate variability, of mean arterial pressure (MAP) and MAP variability was investigated in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and heart rate every 2.5 min in freely moving rats with indwelling arterial catheters. Variability was expressed as the standard deviation in each rat. Heart rate and MAP showed clear diurnal rhythms, both in WKY and SHR. Blood pressure variability was clearly higher in SHR than in WKY, both during dark active hours and during light hours of relative sleep, and it did not change in response to either beta-adrenoceptor or vagal blockade. Structural vascular changes with the consequent increase in vascular reactivity may be one explanation for the elevated blood pressure variability in SHR. Heart rate variability was clearly reduced in SHR compared with WKY. This may be due to a reduced tonic vagal discharge in SHR, whereby a vagally mediated tachycardia is eliminated. The vagal withdrawal is part of the defence reaction, which is more easily elicited in SHR than in WKY.

Animals↗

Analysis of amino acids: neurochemical application.

For high sensitivity analysis of neuroactive amino acids, liquid chromatography employing precolumn derivatisation with o-phthalaldehyde (OPA) is suitable for several reasons. The OPA reagent is non-fluorescent per se, the reaction occurs rapidly in alkaline aqueous solutions and forms highly fluorescent derivatives with primary amines.

Amino Acids↗

Glycoprotein pattern in human brain tumors studied using lectin binding after sodium dodecyl sulfate-gel electrophoresis and protein blotting.

The immunoblotting technique was used to study the glycoproteins in human brain tumor samples including astrocytoma, glioblastoma, meningioma and oligodendroglioma, as well as in normal human brain. Glycoproteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electrophoretically transferred to nitrocellulose membrane and characterized, using binding with 11 different lectins. Tumor-associated glycoproteins were found using the lectins peanut agglutinin (PNA), soybean agglutinin, Limulus polyhemus, Lotus tetragonolobus, Ricinus communis 1, (RCA-1) and wheat germ agglutinin (WGA). Their molecular masses ranged from 50 to 180 kDa. Several of them were common to the 3 types of tumors: astrocytomas, oligodendrogliomas and meningiomas. PNA, RCA-1 and WGA were the 3 most feasible lectins with regard to tumor specificity, simplicity and reproducibility.

Astrocytoma↗