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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Relative role of chloramines, hypochlorous acid, and proteases in the activation of human polymorphonuclear leukocyte collagenase.

The activation of collagenase released by polymorphonuclear leukocytes (PMNs) has been extensively studied in vitro, but the activation of the enzyme in vivo is not fully understood. For further evaluation of the relative role of oxidative and proteolytic mechanisms in the activation of collagenase, PMNs were stimulated by serum-opsonized zymosan under both aerobic and anaerobic conditions. The results showed that similar amounts of collagenase were released by the PMNs under aerobic and anaerobic conditions, but the activity of the released collagenase was twice as high under aerobic conditions as under anaerobic conditions. Under aerobic conditions the enzyme was rapidly activated by hypochlorous acid and chloramines, which are products of the myeloperoxidase-H2O2-chloride system of the PMNs. There was also a slow proteolytic activation of the enzyme, which could be ascribed to cathepsin G and possibly to some other serine proteases of PMNs. When extrapolating these findings to in vivo conditions, it seems probable that the oxidative activation of collagenase will proceed mainly by chloramines, which are more long-lived in the tissue than hypochlorous acid. In poorly oxygenated tissues, collagenase may be mainly activated by proteolytic mechanisms.

Adult↗
PubMed1996

Matching of electron beams for conformal therapy of target volumes at moderate depths.

The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

Biophysical Phenomena↗
PubMed1996

Test procedures for verification of an electron pencil beam algorithm implemented for treatment planning.

The calculation of an electron dose distribution in a patient is a difficult problem because of the presence of tissue and surface inhomogeneities. Verification of the dose planning system is therefore essential. In this investigation, a novel method is used to evaluate a commercially available system (Helax-TMS), at electron energies between 10 and 50 MeV, both for a conventional treatment unit and an MLC-collimated scanned beam unit with a helium-filled treatment head. First, the experiments were designed to verify the local beam database and some fundamental characteristics of the electron beam calculations. Secondly, a number of generalised situations that would be encountered in the clinical treatment planning were evaluated oblique incidence, field shaping with multi-leaf collimator, bolus edges, and air cavities. Dose distributions in two generalised anatomical phantoms simulating a neck and a nose were also analysed. The results have, when so possible, been presented as the dose ratio within the 'flattened area' for dose profiles and down to the 'treatment depth' (80% dose level) for depth doses. In the penumbra region and in the dose fall-off region, the comparison has been represented by the distance deviation between calculated and measured dose profiles or depth doses. A new tool, 'volume integration', was used to evaluate the deviations from a more clinical point of view. Most results were within +/- 2% in dose for volumes larger than a sphere with a diameter of 15 mm, or +/- 2 mm in position. Dose deviations were generally found for oblique incidences and below heterogeneities such as small air cavities and bolus edges in limited volumes.

Algorithms↗
PubMed1996

Correlations of Ki-67 and PCNA to DNA ploidy, S-phase fraction and survival in uveal melanoma.

In 79 patients with uveal melanoma, the tumours were investigated by DNA flow cytometry and immunohistochemical staining of PCNA and Ki-67. S-phase as a continuous variable was significantly correlated with Ki-67 (P = 0.033), but not with PCNA. DNA ploidy was not correlated with either of the two antigens. Ki-67 was significantly correlated with histopathological type (P < 0.001) and tumour size (P < 0.001). Large tumours and epithelioid cell type were associated with a high frequency of Ki-67 positive cells. A high level of Ki-67 positivity (> or = 6.5%) was also associated with a shorter survival (P = 0.0037), and when adjusted for DNA ploidy, histopathological type and tumour size, Ki-67 in the multivariate analysis remained an important prognostic factor (P = 0.017).

Antigens, Neoplasm↗
PubMed1996

Changes of bone mineral mass and soft tissue composition after hip fracture.

The aim of this prospective longitudinal study was to measure prospectively the bone mineral density (BMD) and anthropometric variables after a hip fracture. In particular, we studied changes in the BMD in both the injured and uninjured hips, and examined if the postoperative mortality rate and complications, including pseudarthrosis of the fracture and late segmental collapse of the head of the femur, could be predicted by early bone mass measurements. The bone mineral density and the body composition were measured with dual energy X-ray absorptiometry in 102 consecutive hip fracture patients, 31 men and 71 women, with a mean age of 74 and 79 years, respectively. All cases were operated on within 3 days. The measurements were undertaken within 10 days after the fracture, after 4 and after 12 months. The BMD of the hip fracture cases decreased, especially in the lower extremities where the patients lost 7%, during the first year after the fracture. The patients also lost lean body mass (5%) but gained fat (11%) during the same period. They lost significantly more bone mass in the fractured hip than in the uninjured hip (p < 0.05). No difference was found between those patients who survived and those who died within 2 years after their hip fracture in neither the initial measurement nor in the follow-up measurements. Also, we found no difference between those patients whose hip fracture healed and those who developed late segmental collapse or pseudarthrosis. In conclusion, osteoporotic hip fracture cases lose bone mass at an increased rate, especially in the fractured hip. Also, their soft tissue composition changes, gaining fat while losing muscle mass. Furthermore, it seems that early bone mineral measurements cannot predict postoperative failures or postoperative mortality.

Aged↗
PubMed1996

Theoretical and experimental determination of phantom scatter factors for photon fields with different radial energy variation.

The output factor used for monitor unit determination in radiotherapy can be divided into two factors: the head scatter factor and the phantom scatter factor. Theoretical and experimental phantom scatter factors have been compared for different beam qualities between 4 MV and 50 MV and field sizes from 5 cm x 5 cm to 30 cm x 30 cm. The theoretical data were obtained through a convolution method based on Monte Carlo calculated energy spectra and dose kernels. The calculations have been performed both for accelerators with a rather large energy variation within the field and for accelerators with a constant energy distribution in the field. Deviations between theoretical and experimental data were found to be less than 1%.

Humans↗
PubMed1996

Heat transfer evaluation of the nasal thermistor technique.

When analyzing transvalvular and venous flow velocity patterns, it is important to relate them to respiration. An accurate recording of respiratory phase can be carried out with different methods. One of these methods is the use of a thermistor, which reacts to the variation in air temperature, placed in the noise of the patient. The thermistor used has a diameter for 1.0 mm and is of standard bead type. Although small, it has a considerable long time-constant and a long time-delay. The high time-constant gives a low cutoff frequency, well below the respiratory frequency and thereby causing a large phase difference. The thermistor was analyzed with the lumped heat capacity method, where it was easy to study the influence from design parameters, time-dependent air temperature, and velocity. The analysis was extended using the finite element method and the temperature field in the thermistor and the probe was calculated as a function of space and time. These calculations confirmed the result from the lumped model. The result showed that timing of respiration was not accurately obtained with the thermistor analyzed. To improve the timing, it was necessary either to change the measuring method or to use signal processing in order to achieve faster response.

Blood Flow Velocity↗
PubMed1996

Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes.

Since nitric oxide (NO) has been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were investigated in psoriatic skin by reverse transcriptase coupled to the polymerase chain reaction (PCR). The study showed that the mRNA expression of brain nitric oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic plaques lesions and uninvolved skin, while mRNA transcripts for the second isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the present method. In contrast, the mRNA expression of iNOS was markedly increased in lesional skin as compared to uninvolved skin. Cultured human keratinocytes exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in 24 h, the expression had returned to baseline expression. In summary, the study demonstrates that mRNA for the inducible form of NOS is over-expressed in psoriatic lesions. The cause of this may be the local presence of inflammatory cytokines. These findings imply that iNOS may play an important part in local regulation of NO synthesis in psoriasis and other inflammatory dermatoses.

Adult↗
PubMed1996

Design, synthesis, tandem mass spectrometric sequencing and biological activity of NGF mimetics.

Nine low molecular weight nerve growth factor (NGF)-like peptides have been designed to mimic the putative receptor-binding epitope of NGF defined by two beta-hairpin loops. Eight different spacers were used as variable links between the beta-loop amino acid residues, which from mutagenesis experiments were found to play an important role in the biological activity of NGF. These spacers were amino acids, natural or non-natural, differing in length (5-13 A) and polarity. The peptides were synthesized via the Fmoc solid-phase peptide synthesis and purified by reversed-phase HPLC. Their primary sequences were analyzed by a combination of automated Edman degradation and mass spectrometry. The peptides were tested using two different biological assays, the fibre outgrowth from chick embryonic sympathetic ganglia and the PC12 cell differentiation assay. Weak antagonistic effects could be observed for some peptides.

Adrenal Medulla↗
PubMed1996

Bremsstrahlung production at 50 MeV in different target materials and configurations.

A combination of Monte Carlo, convolution, and experimental techniques have been used to investigate bremsstrahlung production at 50 MeV in full-range targets to produce narrow elementary photon beams for scanning. Calculations using the ITS 3.0 Monte Carlo system for various target designs, including particle transport through the treatment head of an MM5O racetrack microtron and a water phantom, have been compared to experimental dose profiles from narrow photon beams at 10-cm depth in water. A reduction in the ITS 3.0 default substep size has been found necessary even for incomplete agreement, in consistency with the findings of Faddegon and Rogers [Nucl. Instrum. Meth. A 327, 556-565 (1993)] for a different experimental setup and energy using the previous version of ITS. Results show that the calculated shape of the tail of dose distributions from narrow photon beams agrees well with measurements, but CYLTRAN/ITS 3.0 fails to reproduce the central part of the distribution. The discrepancy at small angles, reported previously for EGS4 and ITS 2.1 simulations, possess a limitation to Monte Carlo simulations of narrow photon beams used in scanned systems of clinical accelerators. Radial dose profiles have been calculated by convolution of the energy fluence at the exit of the target with one polyenergetic Monte Carlo calculated dose kernel and also a database consisting of ten different dose kernels corresponding to different monoenergetic photon pencil beams for comparison. The agreement with the much slower fully detailed Monte Carlo calculations was better when using the database kernels than the polyenergetic kernel. Results for the mean energy, mean polar angle, and energy fluence at different depths within various targets have been obtained. These are discussed in the context of the design characteristics of bremsstrahlung targets with emphasis on their utilization for scanning photon beam techniques.

Biophysical Phenomena↗
PubMed1996

Electron contamination in clinical high energy photon beams.

The electron contamination in photon beams has been investigated by means of contaminating lepton depth doses and dose profiles in different geometries with two 20 MV beams. Different components of this contamination have been investigated separately by systematically adding contamination to a "clean" reference field. At 20 MV, the air generated electrons were found to be almost negligible compared to the electrons originating from the accelerator head when measurements were performed in standard fields at SSDs between 80 and 120 cm. The total electron part of the depth dose curve was then almost the same, i.e., independent of SSD, when the collimator opening was held fixed. However, when different accessories such as a shaping block and different attenuating plates were located in the beam path below the collimators, a large SSD dependence of the electron contamination was noticed. A comparison was also made between two machines, one equipped with a multileaf collimator, with similar beam qualities at 20 MV. These measurements indicate that the interior view of the treatment head seen by the detector (mainly the flattening filter, monitor chamber, or other electron generating material) influences the magnitude of the electron contamination. When the collimator opening is decreased the electron contamination will also decrease as parts of the electron source will be shielded by the collimator blocks.

Air↗
PubMed1996

Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients.

The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (Ka). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of Ka for patients with high bilirubin levels ( > 1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of Ka was 0.957 h-1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for Ka. Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary.

AIDS-Related Opportunistic Infections↗
PubMed1996

Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis.

Concentrations of doxycycline and penicillin G in serum and cerebrospinal fluid (CSF) were analyzed in 46 patients during treatment for neuroborreliosis. Twenty patients were treated intravenously with penicillin G at 3 g every 6 h (q6h), and 26 patients were treated orally with doxycycline at 200 mg q24h. All samples were collected on day 13 of treatment. The median concentrations of penicillin G in serum were 0.5, 37, and 5.6 micrograms/ml before and 1 and 3 h after drug administration, and that in CSF was 0.5 (range, 0.3 to 1.6) microgram/ml after 2 to 3 h. The median concentrations of doxycycline in serum were 2.1, 6.1, and 4.7 micrograms/ml before and 2 and 6 h after drug administration, and that in CSF was 0.6 (range, 0.4 to 2.5) microgram/ml after 4 h. All patients had concentrations of penicillin G or doxycycline in CSF above the lowest reported MICs of penicillin G (0.003 microgram/ml) and doxycycline (0.12 microgram/ml) for Borrelia burgdorferi. However, no patients had a drug concentration in CSF above the highest reported MIC of penicillin G (8 micrograms/ml), and only one had a drug concentration in CSF above the highest reported MIC of doxycycline (2 micrograms/ml), despite good clinical response to treatment. No treatment failure or relapse was observed during a 1-year follow-up, although one patient treated with penicillin G and one treated with doxycycline were retreated because of residual pain. The chosen dosages of penicillin G and doxycycline seem to give sufficient concentrations in serum and CSF for the treatment of neuroborreliosis.

Adolescent↗
PubMed1996

Busulphan kinetics and limited sampling model in children with leukemia and inherited disorders.

Busulphan pharmacokinetics were investigated in 20 children, who underwent bone marrow transplantation for either leukemia or inherited disorders. Busulphan (1.90-6.02 mg/kg/day) was administered orally as a single dose or twice daily. Busulphan kinetics were found to be linear within the studied range. Children with inherited disorders eliminated busulphan significantly faster after the first and the last dose with half-lives (t1/2) of 1.93 and 1.71 h, respectively compared to children with leukemia (3.16 and 2.70 h, respectively). The area under plasma concentration curves (AUCs, corrected for mg/kg) as an expression for the systemic exposure of busulphan were significantly higher in children with leukemia, 22.4 and 19.04 mumol/l.h (5527 and 4690 ng.h.ml-1) after the first and the last dose, respectively, compared to 11.2 and 8.2 mumol/l.h (2768 and 2029 ng.h.ml-1) found in children with inherited disorders. The present results confirm those reported by others, ie busulphan pharmacokinetics can be influenced by the underlying disease and its status. Our population pharmacokinetic analysis showed a negative correlation between the weight corrected clearance and the age in both groups of children. However, clearance was about 42% higher in children with inherited disorders compared to those with leukemia. To estimate AUC for the first dose, we evaluated a limited sampling model based on three concentrations (1, 3 and 6 h). A high correlation (r = 0.998, P < 0.0001, n = 40) between the estimated and the determined AUC was found. The present model is reliable and adequate for studying more patients, with a long-term follow-up combined with drug monitoring in correlation with drug efficacy and toxicity to define the optimal busulphan dosage required.

Administration, Oral↗
PubMed1996

Cloning and sequencing of cDNAs encoding ribonucleotide reductase from zebrafish Danio rerio.

We have cloned and sequenced cDNAs coding for the R1 and R2 proteins of ribonucleotide reductase from zebrafish (Danio rerio). This ribonucleotide reductase shows high amino acid sequence identity to those of other vertebrates. The R1 cDNA has a coding sequence of 2382 bp, yielding a 794 amino acid protein, and the R2 cDNA has a coding sequence of 1158 bp, yielding a 386 amino acid protein. The zebrafish R1 shows 94% similarity and R2 shows 91% similarity to the human R1 and R2, respectively. The similarity extends to intron positions, of which the equivalent of mouse R2 intron 3 has been studied.

Amino Acid Sequence↗
PubMed1995

DNA ploidy and S-phase fraction as prognostic factors in patients with uveal melanomas.

In 96 patients with uveal malignant melanomas the tumours were investigated by DNA flow cytometry. Thirty-eight per cent of the melanomas were aneuploid. By univariate analysis significant correlations with survival were found for histological type, tumour size, DNA ploidy, evidence of 'blind eye' and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be histological type (P = 0.0008), tumour size (P < 0.0001) and DNA ploidy (P = 0.0038). Evidence of 'blind eye' was not significantly correlated with survival after adjustments for the other variables mentioned above. The S-phase fraction could be estimated in all 60 diploid tumours and in 12 of 36 aneuploid melanomas. By univariate analysis this variable was found to be a significant prognostic factor, but did not remain so after adjustment for ploidy, histological type and tumor size. We further conclude that patients with small DNA diploid uveal melanomas of spindle cell type have a rather favourable prognosis.

Adult↗