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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Influence of electron contamination on in vivo surface dosimetry for high-energy photon beams.

The influence of the electron contamination at in vivo dosimetry with diodes on the patient surface has been investigated by introducing different accessories in the beam path and by changing the field size and SSD. The results show a clear correlation between the electron contamination at an effective measuring depth of the diode and the signal from the patient diode. When the electron contamination is taken into account the agreement between the diode values and the absorbed dose is greatly improved. More accurate in vivo dosimetry with less error margins is therefore possible if better predictions of the electron contamination in high-energy photon beams can be performed.

Biophysical Phenomena↗
PubMed1998

Relation between putative afferent axons and the glia limitans in rat motor roots.

The law of Magendie states that ventral roots channel efferent axons from the spinal cord to the periphery, while dorsal roots channel afferent axons from the periphery into the spinal cord. As primary afferent C-fibres occur in mammalian ventral roots, this law has been questioned. However, other observations suggest that ganglionic axons do not enter the spinal cord via ventral roots. The present paper examined, by double labelling immunohistochemistry, the relation between putative peripheral afferents and the PNS/CNS transition in the trigeminal motor root and in selected spinal ventral roots of the rat. The afferents were labelled with antibodies against vasoactive intestinal polypeptide, substance P or calcitonin gene-related peptide. The glia limitans at the PNS/CNS transition was defined with antibodies against glial fibrillary acidic protein. The results showed that no immunoreactive axons occurred in the trigeminal motor root. However, in all ventral roots examined, labelled axons were frequently observed. While some of these ended blindly, looped or branched in the rootlets, others shifted to the pia mater. Immunoreactive axons crossing the glia limitans at the PNS/CNS transition were not observed. Thus, the results obtained support the law of Magendie.

Animals↗
PubMed1997

cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases.

Monoglyceride lipase catalyzes the last step in the hydrolysis of stored triglycerides in the adipocyte and presumably also complements the action of lipoprotein lipase in degrading triglycerides from chylomicrons and very low density lipoproteins. Monoglyceride lipase was cloned from a mouse adipocyte cDNA library. The predicted amino acid sequence consisted of 302 amino acids, corresponding to a molecular weight of 33,218. The sequence showed no extensive homology to other known mammalian proteins, but a number of microbial proteins, including two bacterial lysophospholipases and a family of haloperoxidases, were found to be distantly related to this enzyme. By means of multiple sequence alignment and secondary structure prediction, the structural elements in monoglyceride lipase, as well as the putative catalytic triad, were identified. The residues of the proposed triad, Ser-122, in a GXSXG motif, Asp-239, and His-269, were confirmed by site-directed mutagenesis experiments. Northern blot analysis revealed that monoglyceride lipase is ubiquitously expressed among tissues, with a transcript size of about 4 kilobases.

Adipocytes↗
PubMed1997

Depth for dose calibration in high energy photon beams.

BACKGROUND AND PURPOSE: The normalisation depth for determination of output factors in photon fields has frequently been the depth of dose maximum. At high energies the contribution from contaminating electrons is significant at dose maximum and is critically dependent on the beam geometry parameters, which is why a larger depth should be preferred. MATERIALS AND METHODS: The effect of electron contamination was studied using a purging magnet to remove charged particles from the treatment head and a helium bag to minimise production between the head and the phantom. RESULTS: A depth of 10 cm was found to be beyond the range of the contaminating electrons for photon energies up to 20 MV (TPR(20)(10) = 0.772). However, at 50 MV (TPR(20)(10) = 0.810) contaminating electrons contribute 2-3% to the absorbed dose at 10 cm depth. CONCLUSIONS: 10 cm is recommended as both reference and normalisation depth for all megavoltage photon beam qualities, i.e. 60Co and X-rays from accelerators up to 50 MV.

Calibration↗
PubMed1997

Exploration of new treatment modalities offered by high energy (up to 50 MeV) electrons and photons.

BACKGROUND AND PURPOSE: A number of deep seated tumours are difficult to treat conformally with photon beams mainly due to the almost exponential dose decrease with depth. MATERIALS AND METHODS: In order to improve the conformity of these treatments a number of useful characteristics of high energy (above 20 MeV) electron beams of the MM50 Racetrack Microtron have been systematically investigated and clinically applied. RESULTS: A typical characteristic of electron beams with energies up to 20 MeV is the sharp dose fall-off with depth. At higher energies this effect is less pronounced but may be improved by adding a small fraction of photons with a matching dose gradient (wedge). With this technique, high energy electrons can be used close to sensitive organs down to 17 cm depth. Another physical characteristic of high energy electrons is the sharp penumbra at depths down to 4-5 cm and the possibility to use opposed electron beams in order to enhance the dose centrally or near the centre of a body. Skin sparing by delivering a part of the absorbed dose with photons through the same beam portal as the electrons has also been systematically studied. These characteristics of the high-energy electron beams have been utilised in the optimisation of some clinical treatments. CONCLUSIONS: Electron beams in this high energy region give increased possibilities to achieve dose conformity. Enhanced conformity can be obtained especially if electrons and photons are combined to augment some specific characteristics of the electron beams.

Dose-Response Relationship, Radiation↗
PubMed1997

Semi-conductor detectors in output factor measurements.

BACKGROUND AND PURPOSE: Output factors are generally measured with cylindrical ionization chambers. It was investigated if Si-diodes of p-type instead could be used. The advantage would be the small detector size and the robust construction of the detector. MATERIALS AND METHODS: Two types of diodes were studied, one with a shielding layer of tungsten specially made to reduce the excess response for scattered photons and one standard diode without any extra shielding. The measurements were performed at accelerating potentials between 4 and 50 MV and beam sizes between 4 cm x 4 cm and 40 cm x 40 cm. RESULTS: The results showed that both types of diodes are suitable for measurements of head scatter factors in mini-phantoms. However, the diodes were found inappropriate for measurement of output factors for large fields in extended water phantoms. For small fields (<10 cm x 10 cm) a small detector is advantageous and no errors due to the scatter contribution were seen. CONCLUSIONS: An cylindrical ionization chamber is the best choice for output factor measurements in extended water phantoms for large field sizes while diodes are an alternative in small fields. There were negligible differences between the detectors in head scatter measurements in mini phantoms.

Humans↗
PubMed1997

Ganglionic axons in motor roots and pia mater.

In addition to motor axons and preganglionic axons, ventral roots contain unmyelinated or thin myelinated sensory axons and postganglionic sympathetic axons. It has been said that ventral roots channel sensory axons to the CNS. However, it now seems that these axons end blindly, shift to the pia or loop and return towards the periphery and that these units reach the CNS via dorsal roots. Sensory ventral root axons project from a variety of somatic or visceral receptors; some of them are third branches of dorsal root afferents and some seem to lack a CNS projection. Many ventral root afferents contain substance P (SP) and/or calcitonin gene-related peptide (CGRP). These fibres are not affected by neonatal capsaicin treatment and they cannot induce radicular or pial extravasation. Some thin ventral root axons are sympathetic and relate to blood vessels. Afferents containing SP and/or CGRP and sympathetic axons also occur in the spinal pia mater. The sensory axons mediate pain. They might also have vasomotor, tissue-regulatory and/or mechanoreceptive functions. The motor roots of cranial nerves IV, VI and XI contain unmyelinated axons arranged like in ventral roots outside the autonomic outflow. However, the motor root of cranial nerve V channels some unmyelinated axons into the CNS. The occurrence of thin axons in ventral roots and pia mater changes during development and ageing. After peripheral nerve injury, ipsilateral ventral roots and pia are invaded by new sensory and postganglionic sympathetic axons.

Animals↗
PubMed1997

Implementation of Varian's EDW 5.2 on a Clinac 2300C/D for use with Helax TMS 3.1 dose planning system.

An EDW field is in principle a sum of fields with different sizes. The Helax TMS 3.1 dose planning system uses pre-existing open beam data and information specific to the geometry of the accelerator treatment head including flattening filter and collimators to generate open fields. These open fields are then summed using the Segmented Treatment Tables (STT) to generate the Enhanced Dynamic Wedge fields. Verification of predicted fields and output factors against measured data are discussed for different wedge angles, asymmetric fields and shaped fields.

Algorithms↗
PubMed1997

Transperitoneal or totally extraperitoneal approach in laparoscopic hernia repair: results of 491 consecutive herniorrhaphies.

Laparoscopic hernia surgery was introduced in this unit in May 1992. Up to November 1995, 426 patients with 491 inguinal and femoral hernias have undergone surgery. A transabdominal preperitoneal (TAPP) approach was used in 339 patients with 393 hernias. After June 1994 a totally extraperitoneal (TEP) technique was used in 87 patients with 98 hernias. This prospective nonrandomized study deals with the learning curve, complications, and early results. The mean (SD) follow-up times in the TAPP and TEP groups were 23 (9) and 7 (4) months, respectively. Mean operating times and hospital stays did not differ between the TAPP and TEP patients, but the period off work was shorter in the TEP group. Fifteen major complications, including one postoperative death, two bowel obstructions, one severe neuralgia, three trocar hernias, one epigastric artery bleeding episode, and seven recurrences, were recorded; all except one was in the TAPP group. The TEP operation may be the method of choice in laparoscopic hernia surgery.

Abdomen↗
PubMed1997

Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.

Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. In this study the possible interactions between levosimendan and ethanol in human have been studied. Twelve healthy male volunteers were included in this double-blind, randomized, cross-over study. The study consisted of three treatment periods: levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and ethanol concentrations were collected for 8 h after the dosing. To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for subjective assessment of performance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the pharmacokinetics of levosimendan except the volume of distribution of central compartment which was decreased. Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.

Adult↗
PubMed1996

Hormone-sensitive lipase is structurally related to acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. Building of a three-dimensional model for the catalytic domain of hormone-sensitive lipase.

Hormone-sensitive lipase is the key enzyme in the mobilization of fatty acids from adipose tissue, thereby playing a crucial role in the overall energy homeostasis in mammals. Its activity is stimulated by catecholamines through cAMP-dependent phosphorylation of a single serine, a process that is prevented by insulin. This regulatory property is unique to this enzyme among all known lipases and has been acquired during evolution through insertion of a regulatory module into an ancestral lipase. Sequence alignments have failed to detect significant homology between hormone-sensitive lipase and the rest of the mammalian lipases and esterases, to which this enzyme is only very distantly related. In the present work, we report the finding of a remarkable secondary structure homology between hormone-sensitive lipase and the enzymes from a superfamily of esterases and lipases that includes acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. This finding, based on the identification of the secondary structure elements in the hormone-sensitive lipase sequence, has allowed us to construct a three-dimensional model for the catalytic domain of hormone-sensitive lipase. The model reveals the topological organization, predicts the components of the catalytic triad, suggests a three-dimensional localization of the regulatory module, and provides a valuable tool for the future study of structural and functional aspects of this metabolically important enzyme.

Acetylcholinesterase↗
PubMed1996

Postnatal development and aging of the rat ventral root L5: electron microscopic and immunohistochemical studies.

The ventral root L5 of neonatal and adult rats has been used in many experimental studies on ganglionic C-fibers. Since the normal presence of such axons in L5 roots from animals of different ages is unknown, the results of these studies cannot be appropriately interpreted. In the present study we examine L5 ventral roots from developing and aging rats in this respect. Electron microscopic examination revealed that C-fibers occur in neonatal roots. The adult proportion has been established at day 30. Immunohistochemical analysis showed that thin ganglionic fibers with substance P/calcitonin gene-related peptide- or tyrosine hydroxylase-like immunoreactivity in the L5 root and the spinal pia mater seem to increase postnatally from low levels at birth. In roots from aged rats, myelinated fibers with a variety of aberrant features occur in normal numbers. The occurrence of unmyelinated axons is elevated. The increased presence of fibers with calcitonin gene-related peptide- or tyrosine hydroxylase-like immunoreactivity in aged roots indicates that the extra unmyelinated fibers may represent motor sprouts and sympathetic fibers, respectively. We conclude that the rat ventral root L5 contains a variable number of putative sensory and sympathetic axons at all ages.

Adrenergic Fibers↗
PubMed1996

Sheath lengths of large motor axons in the ventral root L5 of neonatal and adult rats.

This study examines the developmental sheath elongation in the rat ventral root L5. Electron microscopic analysis of serial transverse sections through roots from newborn rats shows an average internuclear distance (IND) of 66 microns (calculated fresh length 73 microns). Light microscopic analysis of teased adult roots shows that the largest fibers have an average internodal length of some 1250 microns at 5 months. Hence, large fibers exhibit a developmental sheath elongation of 17 times. The ventral root L5 elongates 11 times only. This mismatch necessitates a myelin sheath remodelling.

Aging↗
PubMed1996

Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma.

DNA ploidy and S-phase fraction were measured by flow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases only the primary tumours or the last metastases could be evaluated. There was a significantly higher mean S-phase value in melanoma metastases from patients with complete or partial responses compared with patients with progressive disease. Neither the S-phase fraction of the primary tumour, nor the DNA ploidy of the primary tumour or of the last histologically verified metastases taken before inclusion into the study were associated with therapeutic response. In the multivariate analysis, both the anatomical location of the metastases and the S-phase fraction measured on the last metastases remained significant prognostic factors of response. In the univariate survival analysis, there was an association between high S-phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S-phase fraction, the number of involved metastatic sites and the treatment response were independent predictive factors. We conclude that, in disseminated melanoma treated with chemotherapy, a high S-phase fraction measured in the last histologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S-phase measurement as a potential tool for selecting patients for treatment.

Adolescent↗
PubMed1996

Enantiomeric bioanalysis of simendan and levosimendan by chiral high-performance liquid chromatography.

rac-Simendan, (+/-)-(R,S)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-phenyl ] hydrazono]propanedinitrile, and the levorotatory enantiomer levosimendan, are drug candidates intended for the treatment of congestive heart failure. An enantiospecific high-performance liquid chromatographic (HPLC) method suitable for determination of the ratio of the enantiomer concentrations in blood plasma samples was developed. Direct resolution of the enantiomers was achieved by using a chiral beta-cyclodextrin stationary phase in reversed phase mode. With an eluent containing 24-33% of methanol in a 0.5% (v/v) triethylammonium acetate buffer, pH 6.0, and a flow rate of 1 ml/min, a resolution (1.2-1.6) adequate for the determinations was achieved. By using UV detection, the relative concentration of the enantiomers in plasma was assessed down to 10 ng/ml. For the racemate, the results indicated a slightly enantioselective disposition and plasma protein binding in rat, dog, and man. The pure enantiomer, levosimendan, was found not to isomerize in vivo.

Animals↗