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Biomedical subjects

M Sandström

Publications and source records attributed to M Sandström.

At least 19 recordsLinked to original sources

Population analysis of the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients.

PURPOSE: The aims of the study were (a) to characterise the pharmacokinetics (PK), including inter-individual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and (b) to characterise the relationship between the PK and the haematological toxicity of the component drugs of the fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast cancer patients. PATIENTS AND METHODS: Data from 140 breast cancer patients, either within one of different studies or in routine clinical management, were included in the analyses. The patients were all treated with the fluorouracil-epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses, either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP, respectively, or according to a dose escalation/reduction protocol (tailored dosing). PK data were available from 84 of the patients, whereas time-courses of haematological toxicity were available from 87 patients. The data analysis was carried out using mixed effects models within the NONMEM program. RESULTS: The PK of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of CP, were described with a one-compartment model with saturable elimination, a three-compartment linear model and a two-compartment linear model, respectively. No clinical significant correlation was found between PK across drugs. The unexplained variability in clearance was found to be less within patients, between courses (inter-occasion variability, IOV) than between patients (inter-individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV diminished by approximately 45% when significant covariates were included and the final population model predicts an IIV that is equal to IOV. Significant covariates for elimination capacity parameters were serum albumin (5-FU, EPI and 4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA) (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for none of the studied drugs did body weight explain the PK variability. The time-course of haematological toxicity after treatment was well described by a semi-physiological model that assumes additive haematological toxicity between CP and EPI with negligible contribution from 5-FU. The influence of G-CSF could be incorporated into the model in a mechanistic manner as shortening the maturation time to 43% of the normal duration and increasing the mitotic activity to 269% of normal activity. CONCLUSIONS: The models presented describe the dose-concentration-toxicity relationships for the FEC therapy and may provide a basis for implementation and comparison of different individualisation strategies based on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback. The PD model extends on previous semi-mechanistic models in that it also takes G-CSF administration into account.

Antineoplastic Combined Chemotherapy Protocols↗

Model describing the relationship between pharmacokinetics and hematologic toxicity of the epirubicin-docetaxel regimen in breast cancer patients.

PURPOSE: The aims of the present study were (1) to characterize the pharmacokinetics of both component drugs and (2) to describe the relationship between the pharmacokinetics and the dose-limiting hematologic toxicity for the epirubicin (EPI)/docetaxel (DTX) regimen in breast cancer patients. PATIENTS AND METHODS: Forty-four patients with advanced disease received EPI and DTX every 3 weeks for up to nine cycles. The initial doses (EPI/DTX) were 75/70 mg/m(2). Based on leukocyte (WBC) and platelet counts, the subsequent doses were, stepwise, either escalated (maximum, 120/100 mg/m(2)) or reduced (minimum, 40/50 mg/m(2)). Hematologic toxicity was monitored in all patients, whereas pharmacokinetics was studied in 16 patients. A semiphysiological model, including physiological parameters as well as drug-specific parameters, was used to describe the time course of WBC count following treatment. RESULTS: In the final pharmacokinetic model, interoccasion variability was estimated to be less than interindividual variability in the clearances for both drugs. The sum of the individual EPI and DTX areas under concentration-time curve correlated stronger to WBC survival fraction than did the corresponding sum of doses. A pharmacokinetic-pharmacodynamic (PK-PD) model with additive effects of EPI and DTX could adequately describe the data. CONCLUSION: The final PK-PD model might provide a tool for calculation of WBC time course, and hence, for prediction of nadir day and duration of leukopenia in breast cancer patients treated with the EPI/DTX regimen.

Adult↗

The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model.

Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg(-1)) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

Animals↗

Population pharmacokinetic modelling of unbound and total plasma concentrations of paclitaxel in cancer patients.

The aim of this study was to validate and further develop a mechanism-based population pharmacokinetic model for paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ, USA) based on the knowledge of Cremophor EL (CrEL) micelle entrapment and to evaluate the exposure/toxicity relationships. Paclitaxel (total and unbound) and CrEL concentrations were obtained according to a sparse sampling scheme with on average only 3.5 samples per course from 45 patients with solid tumours who received 3-hour infusions of paclitaxel (final dose range 112-233 mg/m(2)). The present data were predicted well by the mechanism-based model. In addition, bilirubin and body size were found to be significant as covariates. A change in body surface area (BSA) of 0.1 m(2) typically caused a change in clearance (CL) of 22.3 l/h and an increase in bilirubin of 10 microM typically caused a decrease in CL of 41 l/h. Toxicity was best described by a threshold model. In conclusion, even with a sparse sampling scheme, the same mechanism-based binding components as in the previously developed model could be identified. Once the CrEL and total paclitaxel plasma concentrations are known, the unbound concentrations, which are more closely related to the haematological toxicity, can be predicted.

Adult↗

Crystal and solution structures of N,N-dimethylthioformamide-solvated copper(I), silver(I), and gold(I) ions studied by X-ray diffraction, X-ray absorption, and vibrational spectroscopy.

Crystal structures of the solvated copper(I) and silver(I) perchlorate salts crystallizing from N,N-dimethylthioformamide solution have been determined by single-crystal X-ray diffraction at 295 K. Tetrakis(N,N-dimethylthioformamide)copper(I) perchlorate, [Cu(SCHN(CH(3))(2))(4)]ClO(4), crystallizes in the monoclinic space group P2/n (No. 13) with a = 8.428(2), b = 9.605(2), and c = 15.096(3) A, beta = 104.35(2) degrees, and Z = 2. The copper(I) ion in a site of C(2) symmetry coordinates four N,N-dimethylthioformamide ligands in a slightly distorted tetrahedral coordination with Cu-S bond distances of 2.3249(8) and 2.3494(8) A. The triclinic (P1, No. 2) tris(N,N-dimethylthioformamide)silver(I) perchlorate, Ag(SCHN(CH(3))(2))(3)ClO(4), with a = 7.4149(5), b = 7.7953(5), and c = 17.1482(1) A, alpha = 98.341(5), beta = 93.910(5), and gamma = 107.084(5) degrees, and Z = 2, contains centrosymmetric Ag(2)(SCHN(CH(3))(2))(6)(2+) dimers in which two almost planar AgS(3) units are held together by an asymmetric double sulfur bridge with one short and one long Ag-S bond, 2.529(1) and 2.930(1) A, respectively. The Ag-S bond distances to the two terminal N,N-dimethylthioformamide ligands are 2.469(1) and 2.543(1) A. The solvated copper(I) and silver(I) ions in solution were found by means of large-angle X-ray scattering (LAXS) to coordinate four N,N-dimethylthioformamide molecules with the mean Cu-S and Ag-S bond distances 2.36(1) and 2.58(1) A, respectively, probably with distorted tetrahedral coordination geometry, while an EXAFS study gave the Cu-S bond distance 2.34(1) A. EXAFS studies showed a linear S-Au-S entity with an Au-S bond distance of 2.290(5) A in the structure of the solid bis(N,N-dimethylthioformamide)gold(I) tetrafluoroborate, Au(SCHN(CH(3))(2))(2)BF(4). The structure in solution is similar with a mean Au-S bond distance of 2.283(4) A. Raman and infrared vibrational spectra of the solvated copper(I), silver(I), and gold(I) ions in the solid state and N,N-dimethylthioformamide solution have been recorded and assigned.

Absorptiometry, Photon↗

Structure of the dimethyl sulfoxide solvated thallium(III) ion in solution and in the solid state.

The structure and vibrational spectra of the dimethyl sulfoxide solvated thallium(III) ion have been studied in a dimethyl sulfoxide solution and in the solid state. X-ray crystallography shows a trigonal unit cell, space group R(-)3 (No. 148), for the [Tl(dmso)(6)](ClO(4))(3) compound with Z = 3, a = b = 11.9764(13) [11.8995(9)] A, c = 20.802(2) [20.467(2)] A, and V = 2584.0(5) [2509.9(4)] A(3) at 295 [150] K. The crystal structure comprises a highly symmetric hexakis(dimethyl sulfoxide)thallium(III) ion, with thallium in a (-)3 symmetry site and a Tl-O bond distance of 2.224(3) A at 295 K. The octahedral TlO(6) kernel is compressed along the threefold axis with an O-Tl-O bond angle of 96.20(11) degrees. The Tl-O-S bond angle of 120.7(2) degrees corresponds to a Tl.S distance of 3.292(2) A. One perchlorate ion centered on the (-)3 axis was described by a statistically disordered model. A low-temperature EXAFS study (10 K) resulted in the Tl-O and Tl.S distances of 2.221(4) and 3.282(6) A, respectively, consistent with a Tl-O-S bond angle of 120(1) degrees. The low Debye-Waller factors confirm a regular coordination without the disorder of the dimethyl sulfoxide ligands, which would have resulted from the alternative choice of space group R3 for the crystal structure. Raman and infrared spectra have been recorded and assigned, with the bands at 435 and 447 cm(-)(1) corresponding to the vibrational frequency of the symmetric and asymmetric Tl-O stretching modes, respectively. EXAFS data of a 0.5 mol dm(-3)thallium(III) trifluoromethanesulfonate in a dimethyl sulfoxide solution were consistent with that of a hexasolvated ion with mean Tl-O and Tl.S distances of 2.22(1) and 3.33(2) A, respectively, which correspond to a mean Tl-O-S bond angle of 124(2) degrees. The anomalously large disorder parameter for the Tl-O distances is consistent with a weak pseudo-Jahn-Teller effect. The (205)Tl, (13)C, and (1)H NMR spectra of the complex in solution show single signals at 1886, 39.5, and 2.3 ppm, respectively.

Cations↗

New class of oligonuclear platinum-thallium compounds with a direct metal-metal bond. 5. Structure determination of heterodimetallic cyano complexes in aqueous solution by EXAFS and vibrational spectroscopy.

The structures of three closely related heterodimetallic cyano complexes, [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) (n = 1-3), formed in reactions between [Pt(II)(CN)(4)](2)(-) and Tl(III) cyano complexes, have been studied in aqueous solution. Multinuclear NMR data ((205)Tl, (195)Pt, and (13)C) were used for identification and quantitative analysis. X-ray absorption spectra were recorded at the Pt and Tl L(III) edges. The EXAFS data show, after developing a model describing the extensive multiple scattering within the linearly coordinated cyano ligands, short Pt-Tl bond distances in the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) complexes: 2.60(1), 2.62(1), and 2.64(1) A for n = 1-3, respectively. Thus, the Pt-Tl bond distance increases with increasing number of cyano ligands on the thallium atom. In all three complexes the thallium atom and five cyano ligands, with a mean Pt-C distance of 2.00-2.01 A, octahedrally coordinate the platinum atom. In the hydrated [(NC)(5)Pt-Tl(CN)(H(2)O)(4)](-) species the thallium atom coordinates one cyano ligand, probably as a linear Pt-Tl-CN entity with a Tl-C bond distance of 2.13(1) A, and possibly four loosely bound water molecules with a mean Tl-O bond distance of about 2.51 A. In the [(NC)(5)Pt-Tl(CN)(2)](2)(-) species, the thallium atom probably coordinates the cyano ligands trigonally with two Tl-C bond distances at 2.20(2) A, and in [(NC)(5)Pt-Tl(CN)(3)](3)(-) Tl coordinates tetrahedrally with three Tl-C distances at 2.22(2) A. EXAFS data were reevaluated for previously studied mononuclear thallium(III)-cyano complexes in aqueous solution, [Tl(CN)(2)(H(2)O)(4)](+), [Tl(CN)(3)(H(2)O)], and [Tl(CN)(4)](-), and also for the solid K[Tl(CN)(4)] compound. A comparison shows that the Tl-C bond distances are longer in the dinuclear complexes [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) (n = 1-3) for the same coordination number. Relative oxidation states of the metal atoms were estimated from their (195)Pt and (205)Tl chemical shifts, confirming that the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) complexes can be considered as metastable intermediates in a two-electron-transfer redox reaction from platinum(II) to thallium(III). Vibrational spectra were recorded and force constants from normal-coordinate analyses are used for discussing the delocalized bonding in these species.

Chemical Phenomena↗

Tl-Pt(CN)5 in the solid state--A multimethod study of an unusual compound containing inorganic wires.

The crystal and molecular structure of a polycrystalline powder with a metal-metal bond and the composition TlPt(CN)5 has been determined by combining results from X-ray powder diffraction (XRD), extended X-ray absorption fine structure (EXAFS) and vibrational spectroscopic studies. The XRD data gave the tetragonal space group P4/nmm (No. 129), with a= 7.647(3), c=8.049(3) A, Z=2, and well-determined positions of the heavy metal atoms. The Pt-TI bond length in the compound is 2.627(2) A. The platinum atom coordinates four equivalent equatorial cyano ligands, with a fifth axial CN ligand and a thallium atom completing a distorted octahedral coordination geometry. The Tl-Pt(CN)5 entities are linked together in linear -NC-Pt-Tl-NC-Pt-Tl chains through the axial cyano ligand. These linear "wires" are the essential structural features and influence the properties of the compound. A three-dimensional network is formed by the four equatorial cyano ligands of the platinum atom that form bridges to the thallium atoms of neighbouring antiparallel chains. The platinum atom and the five nitrogen atoms from the bridging cyano groups form a distorted octahedron around the thallium atom. EXAFS data were recorded at the Pt and Tl L(III) edges for a more complete description of the local structure around the Pt and Tl atoms. The excessive multiple scattering was evaluated by means of the FEFF program. Raman and infrared absorption spectroscopy reveal strong coupling of the vibrational modes of the TlPt(CN)5 entities, in particular the metal-metal stretching mode, which is split into four Raman and two IR bands. Factor group theory shows that a structural unit larger than the crystallographic unit cell must be used to assign vibrational bands. Intra- and intermolecular force constants have also been calculated. The compound exhibits red luminescence at 700 +/- 3 nm in glycerol and has a corresponding excitation maximum at 240 nm. X-ray photoelectron spectra (XPS) show that the metal atoms have intermediate oxidation states, Pt3.2+ and Tl1.6-, between those in the parent Pt(II) and Tl(III) species and the decomposition products, Pt(IV) and Tl(I). The solid compound TlPt(CN)5 is stable to 520 degrees C. However in presence of water, a two-electron transfer between the metal atoms results in the cleavage of the metal-metal bond at 80 degrees C, forming a Pt(IV) pentacyanohydrate complex and a monovalent thallium ion.

Crystallography, X-Ray↗

Hydration of some large and highly charged metal ions.

EXAFS studies of metal ions with hydration numbers higher than six in aqueous solution, often show asymmetric distribution of the metal-oxygen bond distances. The hydration number can be determined from a correlation with the bond distance. The mean Ca-O distance 2.46(1) A shows the calcium(II) ion to be eight-hydrated in a wide asymmetric distribution. Theoretically calculated EXAFS oscillations for individual snapshots from an MD simulation show large variations. The scandium(III) ion is surrounded by two groups of about eight water molecules, with the mean Sc-O distance 2.185(6) A. The yttrium(III) ion coordinates eight waters in an asymmetric distribution at 2.368(5) A, and the lanthanum(III) ion 6 + 3 water molecules at 2.52(2) and 2.65(3) A, respectively. For the the uranium(IV) and thorium(IV) ions, the M-O distances 2.42(1) and 2.45(1) A, respectively, indicate hydration numbers close to 10.

Cations↗

Hydration of the calcium ion. An EXAFS, large-angle x-ray scattering, and molecular dynamics simulation study.

The structure of the hydrated calcium(II) ion in aqueous solution has been studied by means of extended X-ray absorption fine structure spectroscopy (EXAFS), large-angle X-ray scattering (LAXS), and molecular dynamics (MD) methods. The EXAFS data displayed a broad and asymmetric distribution of the Ca-O bond distances with the centroid at 2.46(2) A. LAXS studies on four aqueous calcium halide solutions (1.5-2 mol dm(-)(3)) gave a mean Ca-O bond distance of 2.46(1) A. This is consistent with a hydration number of 8 determined from correlations between mean distances and coordination numbers from crystal structures. The LAXS studies showed a second coordination sphere with a mean Ca.O(II) distance of 4.58(5) A, and for the hydrated halide ions the distances Cl.O 3.25(1) A, Br.O 3.36(1) A, and I.O 3.61(1) A were obtained. Molecular dynamics simulations of CaCl(2)(aq) were performed using three different Ca(2+)-OH(2) pair potentials. The potential from the GROMOS program gave results in agreement with experiments, i.e., a coordination number of 8 and an average Ca-O distance of 2.46 A, and was used for further comparisons. Theoretical EXAFS oscillations were computed for individual MD snapshots and showed very large variations, though the simulated average spectrum from 2000 snapshots gave satisfactory agreement with the experimental EXAFS spectra. The effect of thermal motions of the coordinated atoms is inherent in the MD simulation method. Thermal disorder parameters evaluated from simulated spatial atom distribution functions of the oxygen atoms coordinated to the calcium ion were in close agreement with those from the current LAXS and EXAFS analyses. The combined results are consistent with a root-mean-square displacement from the mean Ca-O distance of 0.09(2) A in aqueous solution at 300 K.

Body Water↗

Chromosomal aberrations in peripheral lymphocytes of train engine drivers.

Studies of Swedish railway employees have indicated that railroad engine drivers have an increased cancer morbidity and incidence of chronic lymphatic leukemia. The drivers are exposed to relatively high magnetic fields (MF), ranging from a few to over a hundred microT. Although the possible genotoxic potential of MF is unclear, some earlier studies have indicated that occupational exposure to MF may increase chromosome aberrations in blood lymphocytes. Since an increased level of chromosomal aberrations has been suggested to predict elevated cancer risk, we performed a cytogenetic analysis on cultured (48 h) peripheral lymphocytes of Swedish train engine drivers. A pilot study of 18 engine drivers indicated a significant difference in the frequency of cells with chromosomal aberrations (gaps included or excluded) in comparison with seven concurrent referents (train dispatchers) and a control group of 16 office workers. The engine drivers had about four times higher frequency of cells with chromosome-type aberrations (excluding gaps) than the office workers (P < 0.01) and the dispatchers (P < 0.05). Seventy-eight percent of the engine drivers showed at least one cell per 100 with chromosome-type aberrations compared with 29% among the dispatchers and 31% among the office workers. In a follow-up study, another 30 engine drivers showed an increase (P < 0.05) in the frequency of cells with chromosome-type aberrations (gaps excluded) as compared with 30 referent policemen. Sixty percent of the engine drivers had one or more cells (per 100 cells) with chromosome-type aberrations compared with 30% among the policemen. In conclusion, the results of the two studies support the hypothesis that exposure to MF at mean intensities of 2-15 microT can induce chromosomal damage.

Adult↗

Neurophysiological study of patients with perceived 'electrical hypersensitivity'.

The aim of the present study was to investigate baseline neurophysiological characteristics of the central and autonomous regulation and their reactivity to different tests in a group of persons with so-called 'electrical hypersensitivity', which is often considered as a form of psychosomatic disorders. Twenty patients with combinations of neuroasthenic symptoms (general fatigue, weakness, dizziness, headache) and facial skin (itching, tingling, redness) have been investigated. An equal number of symptom-free persons served as a control group. The examination comprised self-reported measures, testing of visual functions, measurements of blood pressure, heart rate and its variability, electrodermal activity, respiration, EEG and visual evoked potentials (VEP). Several variables were found to differ between the patient and the control groups. The mean value of heart rate in rest condition was higher in the patient group compared to the controls (mean value of inter-beat intervals were 0.80 and 0.90 s, respectively). Heart rate variability and response to standing test were decreased in the patient group compared to the controls. Patients had faster onset, higher amplitudes, and left-right hand asymmetry of the sympathetic skin responses. They had a higher critical fusion frequency (43 vs. 40 Hz), and a trend to increased amplitude of steady-state VEPs at stimulation frequencies of 30-70 Hz. The data indicated that the observed group of patients had a trend to hyper sympathotone, hyperresponsiveness to sensor stimulation and heightened arousal.

Adult↗

Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients.

The aims of the present study were (1) to investigate and quantify the pharmacokinetics, including inter-occasion variability and covariate relationships, of busulphan in BMT patients and (2) to develop a user-friendly initial dosing and therapeutic drug monitoring (TDM) strategy for the treatment of those patients with busulphan. The pharmacokinetics of busulphan was studied in 64 adults and 12 children who received busulphan (1 mg/kg) four times daily for 4 days. A one-compartment model with first order absorption and a lag time was sufficient in describing the concentration-time profile. Oral clearance (CL/F) was found to be correlated to weight (+1.2%/kg), ALT (-13%/microcat/l) and concomitant phenytoin treatment (+21%). CL/F and the volume of distribution (V/F) were estimated to 9.23 l/h and 39.3 l, respectively, in a typical individual. Inter-occasion variability (9.4%) in CL/F was estimated to be less than inter-individual variability (28%), a prerequisite for the value of TDM. Bayesian CL/F estimates based on three samples were in good accordance with those based on all samples. The final population model was implemented into the program Excel. The resulting flexible and easy to use dosing program might be used for both initial and, requiring only three plasma samples, maintenance dose individualization of busulphan therapy.

Administration, Oral↗

Mobile phone use and subjective symptoms. Comparison of symptoms experienced by users of analogue and digital mobile phones.

In 1995 many people reported symptoms such as headaches, feelings of discomfort, warmth behind/around or on the ear and difficulties concentrating while using mobile phones. The number of complaints was higher for people using the digital (GSM) system, i.e. with pulse modulated fields, than for those using the analogue (NMT) system. Our main hypothesis was that GSM users experience more symptoms than NMT users. An epidemiological investigation was initiated including 6379 GSM users and 5613 NMT 900 users in Sweden, and 2500 from each category in Norway. The adjusted odds ratio did not indicate any increased risk for symptoms for GSM users compared with NMT 900 users. Our hypothesis was therefore disproved. However, we observed a statistically significant lower risk for sensations of warmth on the ear for GSM users compared with NMT 900 users. The same trend was seen in Norway for sensations of warmth behind/around the ear and in Sweden for headaches and fatigue. Factors distinguishing the two systems (radio frequency emission, phone temperatures and various ergonomic factors) may be responsible for these results, as well as for a secondary finding: a statistically significant association between calling time/number of calls per day and the prevalence of warmth behind/around or on the ear, headaches and fatigue.

Adult↗

Provocation study of persons with perceived electrical hypersensitivity and controls using magnetic field exposure and recording of electrophysiological characteristics.

The aim of the present study was to investigate possible neurophysiological effects of intermittent 15 sec on/off cycle, 60 Hz, 10 microT magnetic field exposure on patients with perceived "electromagnetic hypersensitivity" (EHS), and control subjects during rest and performance of a mental arithmetic task. Twenty participants (15 female, 5 male, 31-60 years old, mean 45.8 +/- 0.7 years) were invited from the group of EHS patients. Twenty volunteers (15 female, 5 male, 31-59 years old, mean 45.0 +/- 0.7 years?) served as a control group. The test protocol consisted of a set of examinations: EEG, visual evoked potentials, electrodermal activity, ECG, and blood pressure. The total duration of the test was 40 min, divided into two 10 min rest periods and two 10 min periods of mathematical performance. Magnetic field and sham exposures were presented randomly during these periods, resulting in four different conditions: Field-Rest, Sham-Rest, Field-Math, and Sham-Math. The data showed significant main effects of the Group factor (EHS vs. control subjects) on heart rate (F(1,80) = 20.6; P < 0.01), heart rate spectrum ratio (F(1,80) = 9.5; P = 0.02), and electrodermal activity (F(1,76) = 4.2; P = 0.04), whereas EEG characteristics did not differ between groups. The Condition factor (mathematical task vs. relaxed) showed main effects for heart rate (F(1,80) = 14.8; P < 0.01), heart rate spectrum ratio (F(1,80) = 7.8; P = 0.06), electrodermal activity (F(1,76) = 56.8; P < 0.01), and alpha and theta spectral bands of EEG. Magnetic field exposure did not affect autonomous system or electroencephalographic variables of either group. These data do not indicate that EHS patients or control are affected by low-level 60 Hz magnetic field exposure. However, persons reporting EHS differed from the control subjects in baseline values of investigated physiological characteristics. Perhaps EHS patients have a rather distinctive physiological predisposition to sensitivity to physical and psychosocial environmental stressors.

Adult↗

A preliminary evaluation of a new enzyme immunoassay to detect Chlamydia pneumoniae-specific antibodies.

New enzyme immunoassays (EIAs) for determination of specific IgG, IgA, and IgM antibody titers to Chlamydia pneumoniae were evaluated independently in three research laboratories. Specificity of the EIAs was enhanced by removing LPS from the chlamydial antigen. The performance of these EIAs was evaluated in comparison with the microimmunofluorescence (MIF) test using specimens from: (i) a group of adult patients with community-acquired pneumonia (CAP) previously diagnosed as having an acute chlamydial infection by the complement fixation test or the whole inclusion fluorescence test; (ii) from a group of adult patients with acute respiratory tract infections; and (iii) from a group of young children consecutively presenting with acute respiratory tract infections. The MIF test and the EIAs detected acute infections in paired serum specimens from 12 of 14 patients from the first group. Eleven of these 12 patients were positive in both tests. The MIF test detected seven acute infections in single convalescence serum specimens from eight patients. Two of these were also positive in the EIAs. Paired serum specimens from the second group of adult patients (n=12) were collected during an epidemic of C. pneumoniae. The EIAs detected six acute infections. The MIF test detected two additional patients with acute infections. From the group of young children (n=30), the EIAs detected two patients with acute infections. Our conclusion from this preliminary evaluation is that these EIAs could be useful for laboratory diagnosis of acute C. pneumoniae infections. Comprehensive prospective studies should provide suitable data to calculate the sensitivity, specificity, and predictive values.

Adult↗

Solvation of the bismuth(III) ion by water, dimethyl sulfoxide, N,N'-dimethylpropyleneurea, and N,N-dimethylthioformamide. An EXAFS, large-angle X-ray scattering, and crystallographic structural study.

The structure of the solvated bismuth(III) ion in aqueous, dimethyl sulfoxide, N,N'-dimethylpropyleneurea, and N,N-dimethylthioformamide solution has been studied by means of EXAFS and large-angle X-ray scattering (LAXS). The crystal structures of the solid compounds octakis(dimethyl sulfoxide)bismuth(III) perchlorate, [Bi(OS(CH3)2)8](ClO4)3, hexakis(N,N'-dimethylpropyleneurea)bismuth(III) perchlorate, [Bi(OCN2(CH2)3(CH3)2)6](ClO4)3, and nonaaquabismuth(III) trifluoromethanesulfonate, [Bi(H2O)9](CF3SO3)3 (redetermination), have been determined. The aqueous solutions must be strongly acidic, since the hydrated bismuth(III) ion starts to hydrolyze into Bi6O4(OH)4(6+) complexes already at an excess of strong acid at 1.0 mol.dm-3. For very acidic aqueous perchlorate solutions, the LAXS and EXAFS data gave a satisfactory fit for eight-coordination of the bismuth(III) ion, with a mean Bi-O bond distance of 2.41(1) A. The crystal structure of octakis(dimethyl sulfoxide)bismuth(III) perchlorate shows that the bismuth(III) ion coordinates eight dimethyl sulfoxide molecules via the oxygen atoms in a distorted square antiprismatic configuration. The mean Bi-O bond distance is 2.43 A and the mean Bi...S distance 3.56 A. For the dimethyl sulfoxide solution, the corresponding mean distances were found to be 2.411(6) and 3.535(12) A. The N,N'-dimethylpropyleneurea-solvated bismuth(III) ion is octahedrally coordinated in both solid state and solution with the Bi-O bond distances of 2.324(5) and 2.322(3) A, respectively. The bismuth(III) ion is six-coordinated in the sulfur donor solvent N,N-dimethylthioformamide with a mean Bi-S bond distance of 2.794(8) A. A comparison with the structure of the solvated lanthanum(III) ion shows that the bismuth(III) ion is smaller for all coordination numbers. New effective ionic radii for the bismuth(III) ion in different coordination numbers are proposed, based on results in this study and in the literature.

Bismuth↗