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M Sandström

Publications and source records attributed to M Sandström.

At least 37 records · Page 2Linked to original sources
PubMed2000

Steric effects control the structure of the solvated lanthanum(III) ion in aqueous, dimethyl sulfoxide, and N,N'-dimethylpropyleneurea solution. An EXAFS and large-angle X-ray scattering study.

The structure of the solvated lanthanum(III) ion has been determined in aqueous, dimethyl sulfoxide, and N,N'-dimethylpropyleneurea solution by means of the EXAFS and large-angle X-ray scattering (LAXS) techniques. The close agreement between the EXAFS spectra of solid nonaaqualanthanum(III) trifluoromethanesulfonate and of an aqueous lanthanum(III) perchlorate solution shows that the hydrated lanthanum(III) ion in aqueous solution most probably has the same structure as in the solid, i.e., nine water molecules coordinated in a tricapped trigonal prismatic configuration. The data analysis from EXAFS and LAXS measurements of the aqueous solution resulted in the La-O bond distances 2.52(2) and 2.65(3) A to the water molecules in the prism and the capping positions, respectively. The LAXS study shows a second hydration sphere consistent with approximately 18 water molecules at 4.63(2) A. The EXAFS spectra of solid octakis(dimethyl sulfoxide)lanthanum(III) trifluoromethanesulfonate and a dimethyl sulfoxide solution of this salt are also similar. The data analysis of EXAFS and LAXS measurements assuming eight-coordination around lanthanum yielded an La-O bond distance of 2.50(2) A, and an La...S distance of 3.70(3) A, giving an La-O-S angle of 133(2) degrees. The EXAFS data of an N,N'-dimethylpropyleneurea solution of lanthanum(III) trifluoromethanesulfonate gave the La-O bond distance 2.438(4) A and the La...C distance 3.41(2) A, which correspond to an La-O-C angle of 131(2) degrees. The La-O bond distance is consistent with seven-coordination around lanthanum, on the basis of the variation of the ionic radii of the lanthanum(III) ion with different coordination numbers.

Dimethyl Sulfoxide↗
PubMed2000

p53 splice acceptor site mutation and increased HsRAD51 protein expression in Bloom's syndrome GM1492 fibroblasts.

GM1492 human diploid skin fibroblasts derived from a patient with Bloom's syndrome (BS), lack detectable p53 mRNA and protein as shown by Northern and Western blotting, and express an increased RecA-like activity. Here we demonstrate that the p53 gene is grossly intact in GM1492 cells according to Southern blotting. DNA sequencing did not reveal any mutations in the promoter region of p53. A highly sensitive RT-PCR produced a p53 cDNA fragment that was shorter than expected. DNA sequence analysis of p53 cDNA showed that exon 6 was missing, explaining the shorter PCR product. Furthermore, sequencing of genomic DNA revealed a base substitution at the nucleotide preceding the AG splice acceptor site of intron 5. The omission of exon 6 creates a frameshift at the junction of exons 5 and 7, and a premature stop codon in exon 7. The aberrant transcript is predicted to encode a truncated p53 protein containing 189 amino acid residues. Moreover, Western blotting demonstrated elevated HsRAD51 protein levels in GM1492 cells. The lack of sufficient levels of wild-type p53 and increased levels of HsRad51 protein may contribute to the elevated RecA-like activity in the GM1492 fibroblasts.

Alternative Splicing↗
PubMed2000

Evaluation of drug interactions in the established FEC regimen in primary cultures of tumour cells from patients.

BACKGROUND: Chemotherapy using multi-drug regimens is considered more active than single-agent therapy. This may be due to synergistic interactions or, simply, a higher probability of administering an active agent. We investigated in vitro the type of drug interactions in a recognized regimen in relationship to tumour type and drug sensitivity. PATIENTS AND METHODS: The possibility of synergistic and additive interactions between individual cytotoxic drugs was investigated for the component drugs of the established FEC regimen, i.e., 5-fluorouracil, epirubicin and cyclophosphamide, in 243 patient tumour samples representing various drug sensitivity using the non-clonogenic fluorometric microculture cytotoxicity assay. RESULTS: Using a cell survival of < or = 50% as a limit for drug activity and sample sensitivity, the overall response rates to the most active single drug (Dmax) and the combination were 56% and 64%, respectively, with a distribution among diagnoses similar to that in the clinic. For 86% of the samples there was concordance with respect to judgement of activity using either Dmax or the combination. For samples being sensitive to at least one single drug, 95% were also sensitive to the combination whereas for samples with insignificant Dmax effect, only 2% were sensitive to the combination. In samples with modest Dmax effects, i.e., cell survival in the range > 50%- < or = 80%, 45% responded to the combination. The effect of the combination was generally well predicted from the Dmax effect. CONCLUSIONS: The superior antitumour effect of drug combinations compared with single drugs may be due to the higher chance of selecting an active agent. However, for intermediately sensitive tumours, additional interaction effects of a combination may be of clinical significance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Symptoms experienced in connection with mobile phone use.

Many people in Norway and Sweden reported headaches, fatigue, and other symptoms experienced in connection with the use of a mobile phone (MP). Therefore, we initiated a cross-sectional epidemiological study among 17,000 people, all using an MP in their job. Thirty-one percent of the respondents in Norway and 13% of those in Sweden had experienced at least one symptom in connection with MP use. Next to the sensations of warmth on the ear and behind/around the ear, burning sensations in the facial skin and headaches were most commonly reported. Most symptoms usually began during or within half an hour after the call and lasted for up to 2 h. Relatively few had consulted a physician or been on sick leave because of the symptoms, but about 45% among those with an MP attributed symptom had taken steps to reduce the symptom. These results suggest an awareness of the symptoms, but not necessarily a serious health problem.

Acute Disease↗
PubMed2000

Semiphysiological model for the time course of leukocytes after varying schedules of 5-fluorouracil in rats.

Models of leukopenia after chemotherapy are mainly empirical. To increase the derived models' potential of mechanistic understanding and extrapolation, more physiologically based models are being developed. To date, presented models cannot characterize the often-observed rebound of leukocytes. Therefore, a model able to describe the transient decrease and rebound in leukocytes was developed. Three different dosing regimens of 5-fluorouracil were given to rats. One group received a single dose of 127 mg/kg. The other two groups received two and three injections of 63 mg/kg and 49 mg/kg, respectively, with a 2-day interval. Leukocyte counts were followed for 23 to 25 days after the first dose. Plasma concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic and pharmacodynamic models were developed using NONMEM. 5-Fluorouracil showed one-compartment disposition with capacity-limited elimination. The 49-mg/kg dose injected on three occasions produced the lowest leukocyte count (28% of baseline) and the most prominent rebound of the schedules, despite the fact that the fractionated regimens produced only 52 to 56% of the area under the concentration-time curve from time 0 to infinity in the single-dose group. The final semiphysiological model included two 5-fluorouracil-sensitive and two -insensitive transit compartments as well as a compartment of circulating leukocytes. Second order rate constants from the transit compartments and a negative feedback from the circulating leukocytes to the input of the first sensitive compartment characterized the pronounced changes in leukocyte counts. A posterior predictive check as well as predictions into a new data set showed that our model could well predict the schedule-dependent leukopenic effects of 5-fluorouracil.

Animals↗
PubMed1999

The pharmacokinetics of epirubicin and docetaxel in combination in rats.

PURPOSE: The aim of the present study was to investigate possible pharmacokinetic interactions between epirubicin (EPI) and docetaxel (DTX) in rats. METHODS: Male Sprague Dawley rats (n = 36) were used in the study. They received either DTX (5 mg/kg, n = 9), EPI (3.5 mg/kg, n = 13), or a combination (5 mg/kg + 3.5 mg/kg, n = 14), administered as intravenous bolus doses. Blood samples were collected at various time-points between 3 min and 45 h after dose administration. DTX and EPI plasma concentrations were determined by HPLC analysis. Pharmacokinetic evaluation was carried out using the NONMEM program. RESULTS: A three-compartment model best described the concentration-time profiles for EPI. Clearance (CL), intercompartmental clearances (Q2 and Q3), central (V1) and peripheral (V2 and V3) volumes of distribution were estimated as 3. 57 l/h per kg, 5.01 l/h per kg, 12.48 l/h per kg, 0.805 l/kg, 3.67 l/kg and 158 l/kg, respectively. A two-compartment model was sufficient to describe the DTX data. CL, intercompartmental clearance (Q), V1 and V2 for DTX were estimated as 7.3 l/h per kg, 4. 6 l/h per kg, 0.69 l/kg and 2.6 l/kg, respectively. No significant change in the disposition of either drug was found when they were administered in combination compared to when they were given singly. CONCLUSION: Concurrent treatment with EPI and DTX does not appear to cause any changes in the pharmacokinetics of the drugs in rats.

Animals↗
PubMed1999

Autism and hearing loss.

A group of 199 children and adolescents (153 boys, 46 girls) with autistic disorder was audiologically evaluated. Mild to moderate hearing loss was diagnosed in 7.9% and unilateral hearing loss in 1.6% of those who could be tested appropriately. Pronounced to profound bilateral hearing loss or deafness was diagnosed in 3.5% of all cases, representing a prevalence considerably above that in the general population and comparable to the prevalence found in populations with mental retardation. Hearing deficits in autism occurred at similar rates at all levels of intellectual functioning, so it does not appear that the covariation with intellectual impairment per se can account for all of the variance of hearing deficit in autism. Hyperacusis was common, affecting 18.0% of the autism group and 0% in an age-matched nonautism comparison group. In addition, the rate of serous otitis media (23.5%) and related conductive hearing loss (18.3%) appeared to be increased in autistic disorder. The study emphasizes the need for auditory evaluation of individuals with autism in order to refer those with pronounced to profound hearing loss for aural habilitation and to follow those with mild to moderate hearing loss because of the risk of deterioration.

Adolescent↗
PubMed1998

Steady-state visual evoked potentials to computer monitor flicker.

In the present study, steady-state visual evoked potentials (S-VEP) in response to amplitude-modulated light from a computer monitor (colour sVGA, 15-inch tube) have been examined. S-VEPs to computer monitors with different refresh rates (60 Hz or 72 Hz) and screen brightness (65 cd/m2 or 6 cd/m2) were recorded in 13 subjects with normal or corrected-to-normal vision. EEG samples were amplified, averaged and stored using Cadwell Excel EMG-EP recorder and a regression model was applied for the amplitude analysis. The mean values of S-VEP amplitude at 60 Hz were found to be significantly higher at 60 Hz refresh rate vs. 72 Hz (F1,12 = 14.1; P = 0.003). Effect of screen brightness (F2,24 = 6.5; e = 0.62; P = 0.00075) as well as the interaction effect of refresh rate and screen brightness (F2,24 = 11.6; P = 0.0003) were also found to be significant. Data obtained show that the characteristics of amplitude-modulated light from a computer monitor (frequency, brightness, waveform) are sufficient to elicit S-VEP, and the influence is not only restricted to the peripheral divisions of the visual system as it was shown earlier, but also extends to the central brain structures.

Adult↗
PubMed1997

The psychosocial work environment and skin symptoms among visual display terminal workers: a case referent study.

BACKGROUND: This study is a part of the interdisciplinary project The Office Illness Project in Northern Sweden, which was initiated with a questionnaire study in late 1988. Previously published results from the project have shown that facial skin symptoms reported among visual display terminal (VDT) workers are associated with a number of exogenous factors. This part of the project investigated the relation between the psychosocial work environment and facial skin complaints. METHODS: From an initial questionnaire study among 4943 office workers, 163 VDT workers were selected for a case referent study of facial skin symptoms. The data comprise a self-administered questionnaire filled out by 149 subjects and interviews with representatives of the organizations concerned. RESULTS: Psychosocial conditions, especially lack of social support from co-workers, were associated with an increased risk of reporting skin symptoms. Stratification by sex showed that the associations between some psychosocial factors and health differed between men and women. The results indicate that there might be an interaction between psychosocial factors and electric fields in the workplace which increases the risk of reporting skin symptoms. CONCLUSIONS: This study supports the idea that the aetiological basis of facial skin symptoms among VDT-workers includes physical as well as psychosocial factors, and that the interaction between such factors might be significant in the understanding of skin complaints among VDT workers.

Adult↗
PubMed1997

Neurophysiological effects of flickering light in patients with perceived electrical hypersensitivity.

An increasing number of people in Sweden are claiming that they are hypersensitive to electricity. These patients suffer from skin as well as neurological symptoms when they are near computer monitors, fluorescent tubes, or other electrical appliances. Provocation studies with electromagnetic fields emitted from these appliances have, with only one exception, all been negative, indicating that there are other factors in the office environment that can effect the autonomic and/or central nervous system, resulting in the symptoms reported. Flickering light is one such factor and was therefore chosen as the exposure parameter in this study. Ten patients complaining of electrical hypersensitivity and the same number of healthy voluntary control subjects were exposed to amplitude-modulated light. The sensitivity of the brain to this type of visual stimulation was tested by means of objective electrophysiological methods such as electroretinography and visual evoked potential. A higher amplitude of brain cortical responses at all frequencies of stimulation was found when comparing patients with the control subjects, whereas no differences in retinal responses were revealed.

Adult↗
PubMed1997

Facial skin symptoms in office workers. A five-year follow-up study.

This longitudinal study is a part of the interdisciplinary project. The Office Illness Project in Northern Sweden, which was initiated with a questionnaire study in late 1988. Among 3233 visual display terminal (VDT) workers, an initial case-referent group of 163 individuals was selected. The data acquisition included two questionnaires, assessments at the workplaces, interviews with personnel staff of the organizations concerned, and a clinical examination of the respondents. Subjects participating in the case-referent study 1988 filled out a questionnaire in the beginning of 1994. The primary objective of this study is to discuss changes in and causes of facial skin symptoms among VDT workers in the long term. The results show that (1) facial skin symptoms among VDT workers seem to be of a transitory nature for most of those with isolated skin symptoms, whereas the prognosis for those with a more complex symptom picture is more negative, (2) assumptions that measures taken in the work environment-including those involving the VDT and other electric devices-would have a positive effect on symptoms were not supported, and (3) the strongest external risk indicators for lasting skin symptoms seem to be found in the psychosocial work environment. Therefore, one important issue for the understanding of facial skin symptoms is organizational climate and personnel policies. The results also imply that individual factors, both constitutional and psychological, must be considered.

Adult↗
PubMed1996

Lack of relationship between systemic exposure for the component drug of the fluorouracil, epirubicin, and 4-hydroxycyclophosphamide regimen in breast cancer patients.

PURPOSE: The aim of this study was to investigate the covariance between the pharmacokinetics of the three components of the FEC regimen, epirubicin (EPI), fluorouracil (5-FU), and the cyclophosphamide (CP) metabolite 4-hydroxycyclophosphamide (4-OHCP), in breast cancer patients. PATIENTS AND METHODS: Data from 21 women were collected over a total of 35 cycles. 5-FU (300 to 600 mg/m2) and CP (300 to 600 mg/m2) were administered as bolus injections, whereas EPI (15 to 60 mg/m2) was administered either as a bolus injection or as an infusion. The pharmacokinetics of the component drugs were monitored using a limited sampling scheme. Population pharmacokinetic models for each of the three drugs were developed using the program NONMEM. RESULTS: The data for 5-FU were best described by a one-compartment model with nonlinear elimination, where the maximal rate of elimination (Vmax) and the concentration at which the elimination was half-maximal (Km) were 105 mg/L.h and 27 mg/L, respectively. EPI concentration-time profiles showed a triexponential decline, with a mean terminal half-life of 24 hours and a clearance (CL) of 59 L/h. The elimination of 4-OHCP was monoexponential, with a mean half-life of 7 hours. The interindividual coefficients of variation (CVs) in CL were 30%, 22%, and 41% for 5-FU, EPI, and 4-OHCP, respectively. The corresponding values for intrapatient course-to-course variability in CL were 11%, 8%, and 27%. No significant correlation in any of the pharmacokinetic parameters between the drugs was found. CONCLUSION: Individualization of dosing of the FEC regimen using therapeutic drug monitoring and attempts to find concentration-response relationships may be successful, but requires that the exposure of all three drugs is considered simultaneously.

Adult↗
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↗
PubMed1995

Facial skin symptoms in visual display terminal (VDT) workers. A case-referent study of personal, psychosocial, building- and VDT-related risk indicators.

BACKGROUND: The Office Illness Project in northern Sweden, comprising both a screening questionnaire study of 4943 office workers and a case-referent study of facial skin symptoms in 163 subjects was recently completed. Previously published results from the survey showed that female gender, asthma/rhinitis, high psychosocial work load, visual display terminal (VDT) and paperwork were related to an increased prevalence of facial skin symptoms. METHODS: The case-referent study presented in this paper used data from the questionnaire supplemented by information from a clinical examination, a survey of psychosocial factors at work, building data and VDT-related factors from inspection and measurements taken at the work site. RESULTS: Psychosocial conditions and exposure to electromagnetic fields or conditions associated with such factors were related to an increased occurrence of skin symptoms. The results also indicated that personal factors such as atopic dermatitis and physical exposure factors influencing indoor air quality, such as paper exposure and cleaning frequency were related to an increased prevalence of symptoms. CONCLUSIONS: The results suggest that skin symptoms reported by VDT users have a multifactorial background.

Administrative Personnel↗
PubMed1994

Chromosomal aberrations in human amniotic cells after intermittent exposure to fifty hertz magnetic fields.

Our recent studies have shown a significant increase in the frequency of chromosomal aberrations in human amniotic cells after exposure to a sinusoidal 50 Hz, 30 microT (rms) magnetic field. To evaluate further interactions between chromosomes and electromagnetic fields, we have analyzed the effects of intermittent exposure. Amniotic cells were exposed for 72 h to a 50 Hz, 30 microT (rms) magnetic field in a 15 s on and 15 s off fashion. Eight experiments with cells from different fetuses were performed. The results show a 4% mean frequency of aberrations among exposed cells compared to 2% in sham-exposed cells. The difference is statistically significant, with P < 0.05 both excluding and including gaps. In another series of eight experiments, the cells were exposed in the same way but with the field on for 2 s and off for 20 s. Also in these experiments a similar increase in the frequency of chromosomal aberrations was seen, but only when the analysis included gaps. Continuous exposure for 72 h to 300 microT, 50 Hz, did not increase the frequency of chromosomal aberrations. The background electromagnetic fields at different locations within the two incubators used was carefully checked and was nowhere found to exceed 120 nT. Likewise, the background level of chromosomal aberrations in cells cultured at different locations in the incubators showed no significant interculture differences.

Amnion↗
PubMed1994

Altered DNA ligase III activity in the CHO EM9 mutant.

Delayed joining of DNA strand breaks and a high spontaneous level of sister-chromatid exchanges (SCEs) are characteristics of the mutant cell strain EM9 of Chinese hamster ovary (CHO) cells. The introduction of the human gene XRCC1 into EM9 cells reverts the phenotypic properties of EM9 to those of the wild type. We have investigated both DNA ligase activities and a protein which stimulates DNA ligase activity in mutant EM9 cells, XRCC1-transfectant H9T3-7-1 cells and wild-type AA8 cells. Our results, which demonstrate both a decreased DNA ligase activity in EM9 cells using poly(rA).oligo(dT) as substrate and a decreased ability of DNA ligase III to form a covalent DNA ligase III-adenylate intermediate with AMP, clearly indicate an altered DNA ligase III activity in the mutant. Furthermore, the AMP-binding capacity of DNA ligase III and its enzymatic activity with the synthetic polymer were restored after transfection of EM9 with the human XRCC1 gene. Immunoblotting data suggest that the XRCC1 gene does not code for DNA ligase III. In conclusion, the data indicate that the EM9 cell strain has an altered DNA ligase III activity that can be restored by the XRCC1 gene product.

Adenosine Monophosphate↗