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Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 73 records · Page 4Linked to original sources

In vivo testing of the protective efficacy of gloves against allergen-containing products using an open chamber system.

In vitro degradation and permeation testing of glove materials is important in the assessment of the protective efficacy against chemicals. In vivo factors, such as skin-glove contact, skin temperature and humidity may, however, influence the protective effect of the glove. These factors must thus be considered in the overall assessment of a protective glove. An in vivo glove test should as far as possible imitate the practical use of the glove, as well as the exposure to the product/chemical against which the glove should protect. An open chamber system for human in vivo glove testing is presented. This system enables simultaneous testing of 6-8 gloves with 3 provocation times for each glove. Positive controls (no glove) can be included. As a control of the subject's present reactivity to the chemical of interest, conventional patch testing with a dilution series can be performed in parallel. The method is easy to use and convenient for the patient. It promises to be a useful clinical tool in individual preventive measures against contact allergy. The method can be used in glove testing against many hazardous chemicals, both contact allergens and toxic/irritant compounds in workplaces such as the plastics industry and the chemical industry.

Allergens↗

The development of advanced drinking habits in adolescence--a longitudinal study.

This paper aims at exploring the relations between early risk factors and the development of advanced drinking habits in adolescence. Data were derived from the longitudinal research program Individual Development and Adjustment. Results confirm earlier findings from longitudinal studies in this field. Three important factors have been identified: significant others, general sociability, and personality/conduct. More important, though, is that results indicate that knowledge about one or two background characteristics is not enough to make predictions of adolescent drinking habits. Rather, it is the ensemble of circumstances that together lead to an increased risk for advanced drinking habits in adolescence.

Adolescent↗

Lack of drug-drug interaction between three different non-steroidal anti-inflammatory drugs and omeprazole.

OBJECTIVE: To study, in three separate investigations, the potential interaction between omeprazole and three different non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, naproxen and piroxicam) in healthy male and female subjects. METHODS: Each investigation was an open, randomized, three-way cross-over study, in which the subjects were given omeprazole 20 mg once daily for 1 week, the NSAID in therapeutic daily doses (diclofenac 50 mg bid, naproxen 250 mg bid, or piroxicam 10 mg om), or a combination of omeprazole and each NSAID. The plasma concentrations of the NSAID as well as of omeprazole were determined on the last day of each investigation period. RESULTS: None of the NSAIDs studied had any effect on the plasma concentration versus time curve (AUC) of omeprazole. It was also demonstrated that omeprazole 20 mg daily had no significant influence on the pharmacokinetics of the NSAIDs. The AUC ratio, (NSAID +omeprazole):NSAID alone, was 1.11, 0.99, and 0.99 for diclofenac, naproxen, and piroxicam, respectively. CONCLUSION: Diclofenac, naproxen, and piroxicam can be administered together with omeprazole 20 mg daily without need for dosage alteration. There was no significant change in the bioavailability of theses NSAIDs during omeprazole therapy in this study.

Adult↗

HLA-DM is expressed on the cell surface and colocalizes with HLA-DR and invariant chain in human Langerhans cells.

The subcellular distribution patterns of molecules involved in the process of antigen loading [HLA-DR, HLA-DM, and the cytoplasmic and luminal parts of the invariant chain (Ii, CD74)] were investigated in Langerhans cells (LC), both qualitatively and quantitatively. The analysis was performed by immunofluorescence labelling of acetone-fixed vertical cryostat sections from normal human skin specimens and subsequent examination using confocal laser scanning microscopy (CSLM). The intensity-modulated multiple-wavelength scanning (IMS) technique was used to enhance channel separation when scanning dual-labelled specimens. The mean (n = 9) relative epidermal volumes of reactivity were: HLA-DR 8%+/-3%, HLA-DM 6%+/-2%, luminal Ii 6%+/-2%, and cytoplasmic Ii 4%+/-1%. The difference between HLA-DR and the other epitopes was significant at the P<0.001 level. All molecule combinations, except the combination of HLA-DM and luminal Ii (which was not studied), were to various extents colocalized. Experiments performed on unfixed epidermal sheets showed that HLA-DM is present on the cell surface of LC, suggesting that HLA-DM may interact with HLA-DR on the surface to induce peptide loading.

Adult↗

The prognosis of idiopathic choroidal neovascularization in persons younger than 50 years of age.

OBJECTIVE: To examine the prognosis of idiopathic choroidal neovascular membranes in patients younger than 50 years of age at the time of diagnosis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Eighteen consecutive patients from a university clinic (20 eyes) with idiopathic choroidal neovascularization in the macular area. All patients diagnosed between 1979 and 1996 were included; follow-up time varied from 5 to 187 months (mean, 55 months). INTERVENTION: Treatment was conservative. All patients were informed about argon laser photocoagulation, but in the majority of cases, patients were not encouraged to undergo such treatment. Treatment was given on patient's request. MAIN OUTCOME MEASURES: The dimensions of the choroidal neovascular membrane and its distance to the foveola were determined by computerized image analysis and their correlation with final visual acuity determined. RESULTS: Fifteen (75%) of the 20 eyes retained a visual acuity of 20/60 or better. In ten eyes (50%), acuity was 20/25 or better. Six eyes had been treated with laser photocoagulation; only one had a membrane located 200 microns or more from the foveola at the time of treatment. The outcome for treated eyes was no better than for untreated eyes, although the two groups were not directly comparable. In no eye did an initially juxtafoveal or extrafoveal membrane continue to grow under the foveola. CONCLUSIONS: The prognosis of idiopathic choroidal neovascularization was much better than reported previously for eyes with choroidal membranes associated with age-related macular degeneration. A conservative treatment regimen should be considered. The authors have no reason to believe that laser photocoagulation would have improved the outcome in the nontreated eyes.

Adult↗

Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole.

AIMS: To study the pharmacokinetics of three proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole, as well as any potential influence on CYP1A2 activity (measured by means of rate of caffeine metabolism) of these compounds at single dose and repeated dose administration. METHODS: Fourteen healthy males, classified as 12 extensive metabolizers (EMs) and two poor metabolizers (PMs) according to the urinary S/R mephenytoin ratio, completed this open, randomized, three-way cross-over study. In each of the three 7-day treatment periods either omeprazole (20 mg), lansoprazole (30 mg) or pantoprazole (40 mg) in therapeutically recommended doses was administered once daily, and the pharmacokinetics of the proton pump inhibitors as well as the rate of caffeine metabolism was measured on days 1 and 7. RESULTS: In the EMs there was an increase in AUC from day 1 to day 7 for omeprazole. In the PMs the AUC of both omeprazole and lansoprazole was unchanged during repeated dosing, while for pantoprazole there was a tendency to a slight decrease. The AUC at steady state was for all three proton pump inhibitors 5 fold higher in PMs compared with EMs, indicating that the same proportion of the dose, irrespective of compound, is metabolized by CYP2C19. No induction of CYP1A2 was evident for any of the compounds in either EMs or PMs. CONCLUSIONS: The approximately 5 fold difference in AUC between EMs and PMs indicates that approximately 80% of the dose for all three proton pump inhibitors is metabolized by the polymorphically expressed CYP2C19. None of the three proton pump inhibitors, administered in therapeutically recommended doses, is an inducer of CYP1A2--neither in PMs nor in EMs.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Optic neuritis. Doppler ultrasonography compared with MR and correlated with visual evoked potential assessments.

PURPOSE: To establish the role of Doppler ultrasonography (US) in the examination of patients with acute unilateral optic neuritis. MATERIAL AND METHODS: Twenty-five patients with a clinical diagnosis of optic neuritis were prospectively evaluated and 18 of them were included in the study. The inclusion criteria were MR findings of unilateral disease and age below 50 years. All patients were examined with MR in order to objectively detect, localize and measure the optic nerve lesions and in order to exclude patients with unidentifiable optic nerve involvement. Evaluation with US was performed to determine nerve morphology, nerve swelling, and resistance to flow in the central retinal artery. The patients' contralateral optic nerve served as an internal control. The US findings were correlated to the degree of visual impairment, both initially and at follow-up. Visual evoked potential (VEP) assessments were also performed in 16 patients. RESULTS: A statistically significant difference was found in the optic nerve diameter and in the resistance to flow in the central retinal artery between the affected and unaffected eyes. Patients with a prolonged impairment of visual acuity initially had a more swollen nerve and an increased resistance to flow in the affected optic nerve. Prognostic information was also gathered solely by evaluating the unaffected nerve diameter: patients who normally had thinner optic nerves had a more severe form of optic neuritis. VEP assessments were positive in all patients investigated. CONCLUSION: Doppler US can be used together with a VEP assessment as an indicator of the disease process in acute optic neuritis. These methods offer a potential for monitoring patients over time.

Adult↗

Chemotactic peptide-induced activation of Ras in human neutrophils is associated with inhibition of p120-GAP activity.

The monomeric G-protein Ras is now considered to function as an initial regulator of multiple signaling pathways in both normal and transformed cell types. Adhesion and chemoattractant receptors are known to trigger activation of Ras in human neutrophils, but the signaling mechanism that activates Ras has only been partially elucidated. The present results show that in neutrophils, a time- and dose-dependent f-Met-Leu-Phe (FMLP)-induced activation of Ras is mediated by Gi2-proteins, because such activation is inhibited by pertussis toxin and because direct stimulation of heterotrimeric G-proteins with AlF4- is sufficient to activate Ras. Pretreatment of neutrophils with tyrosine kinase inhibitors, i.e. genistein or erbstatin that completely block FMLP-stimulated protein tyrosine phosphorylations, did not affect the FMLP-induced activation of Ras. Moreover, FMLP did not induce any detectable translocation of Grb2 and Sos to the plasma membrane of neutrophils. Other signaling molecules, such as protein kinase C, phosphatidylinositol 3-kinase and Ca2+, do not appear to be involved in the FMLP-induced Ras activation. Instead, stimulation of neutrophils with FMLP or C5a, the latter of which also activates Gi2-proteins, resulted in transient inhibition of the activity of Ras GTPase-activating proteins (GAP) with kinetics that correlated well with the kinetics of Ras activation. Moreover, decreased Ras-GAP activity was found in p120-GAP but not in neurofibromin immunoprecipitates of FMLP-stimulated cells. These results suggest that tyrosine kinase-dependent Ras exchange factors do not contribute to the FMLP-induced activation of Ras but that such activation is mediated via inhibition of p120-GAP in neutrophils.

Adaptor Proteins, Signal Transducing↗

Dual action of cAMP-dependent protein kinase on granulocyte movement.

Cell locomotion is a continuous cycle of integrin-dependent attachments and detachments along chemotactic gradients, driven by dynamic modulations of the actin network. Cyclic AMP (cAMP), which is known to be generated by N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP) receptors but not by beta2 integrins, was investigated as a coordinator of granulocyte locomotion. Elevation of cAMP by exposure to forskolin (100 microM) and 1-isobutyl-methylxanthine (IBMX; 100 microM) caused a marked reduction in beta2 integrin-induced polymerisation of actin, but had a less pronounced effect on the fMLP-induced actin response. Pretreatment of cells with rp-adenosine-3',5'-cyclic monophosphorothioate (rp-cAMPS; 50 microM), an inhibitor of the cAMP-dependent protein kinase (cAPK), resulted in a significant increase in the fMLP-induced actin polymerisation response. In agreement with the effect on filamentous actin (F-actin) forskolin and IBMX markedly suppressed the migration of granulocytes towards fMLP. Surprisingly enough, pretreatment of cells with rp-cAMPS inhibited cell movement to the same extent as forskolin and IBMX did. This dual action of cAMP on granulocyte migration suggest an important regulatory mechanism whereby the balance of this intracellular signal results in an optimal locomotory response.

1-Methyl-3-isobutylxanthine↗

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized phase III study.

BACKGROUND AND PURPOSE: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. METHODS: Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. RESULTS: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. CONCLUSIONS: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment.

Adult↗

Determination of tolterodine and the 5-hydroxymethyl metabolite in plasma, serum and urine using gas chromatography-mass spectrometry.

A specific and sensitive capillary gas chromatography-mass spectrometry assay for the determination of tolterodine and the 5-hydroxymethyl metabolite (Labcode DD 01) in plasma, serum and urine is described. Extraction of the analytes was performed with liquid/liquid or solid-phase extraction prior to derivatisation with a silyl reagent. The derivatives were quantified by selected ion monitoring mass spectrometry using deuterium-labelled internal standards. A single level calibration curve was utilised for quantification of plasma, serum and urine concentrations of tolterodine and DD 01. The accuracy (inter- and intra-day) for both analytes was within 87-110% in the range 0.5 and 50 ng ml-1 and precision was better than 90%. Overall, this method was shown to be reliable for pharmacokinetic assays of tolterodine and the metabolite DD 01 in samples from preclinical and clinical studies.

Benzhydryl Compounds↗

Fas receptor is expressed in human lung squamous cell carcinomas, whereas bcl-2 and apoptosis are not pronounced: a preliminary report.

We report a pilot study on the Fas receptor (APO-1, CD95) in vivo in 15 human squamous cell (non-small) carcinomas and ten normal bronchial specimens. The principal aim was to investigate whether the so-called death receptor, Fas, is present in these tumours. Ligation of Fas promptly induces apoptosis, particularly in T Jurkat cells in vitro, and expression of Fas on human cancer would thus theoretically be of great interest. The immunoreactivity for the anti-apoptotic protein Bcl-2 was also investigated, and the degree of apoptosis was evaluated by TdT dUTP nick end labelling (TUNEL) and conventional morphological criteria. Fas was present in all initial tumours but absent in control tissue, that is in the potential precursor cells of bronchial epithelium (P = 0.001). Fas was not detectable after radiotherapy (P = 0.03). We propose that radiotherapy induces an early selection of tumour cells rather than a down-regulation of Fas. Both Bcl-2 and apoptosis (TUNEL) were generally expressed at a modest level. In agreement with other studies, we did not find any significant correlation between Bcl-2 and prognosis, or between Bcl-2 and TUNEL. Hence, in this preliminary report, we have demonstrated Fas receptor in human squamous cell carcinomas in vivo. This is a novel finding, and the apparent absence of Fas after radiotherapy may have important therapeutic implications.

Apoptosis↗

Rater agreement at lung scintigraphy after consensus training.

PURPOSE: Using the PIOPED criteria in the interpretation of lung scintigraphy, perfect agreement between experienced raters with training in consensus interpretation has been demonstrated. In a previous paper we found a kappa value of 0.54 (0.45-0.63) between experienced raters with no experience of interpretation in consensus; this is significantly lower than the perfect agreement described between consensus-trained raters. The purpose of this study was to reinvestigate the same study population with the same raters, but this time after they had undergone consensus training. MATERIAL AND METHODS: Lung scintigrams of 192 patients were reviewed and categorized according to the PIOPED criteria by 2 raters after consensus training. The 2 raters reviewed a training material of 59 cases, which was not part of the study population, in order to reach a full consensus interpretation. RESULTS: After consensus training the kappa value was 0.57 (0.48-0.66). Three cases had a discrepancy of 2 categories (1.6%), and the remaining discrepancies were of one category. CONCLUSION: Consensus training did not significantly improve the agreement rate between experienced raters from different hospitals. A substantial improvement in agreement rates between hospitals may make heavy demands on resources.

Humans↗

Liquid chromatographic sample cleanup coupled on-line with gas chromatography in the analysis of beta-blockers in human serum and urine.

An on-line coupled reversed-phase liquid chromatographic-gas chromatographic (LC-GC) method with minimal manual sample preparation is developed for the analysis of metoprolol, oxprenolol, propranolol, timolol, and codeine (as an internal standard) in human serum and urine. The method is based on a loop-type interface and concurrent eluent evaporation technique. On-line liquid-liquid extraction (LLE) is used to extract the analytes from aqueous eluent to organic solvent before injection onto the GC, and the two phases are separated with a sandwich-type phase separator. The LC is used for cleanup, and the GC is used for the final separation and detection of the analytes. Total analysis time is less than 45 min, which is much less than those of traditional analysis methods. Recoveries in LC cleanup and on-line LLE are excellent. A marked increase in the recoveries with on-line LLE is obtained by heating the aqueous eluent and the extraction coil. Linearity and repeatability of the method are good for both serum and urine, and the limits of quantitation for the analytes are 18-44 ng/mL.

Adrenergic beta-Antagonists↗

A comparison between one and three years of treatment in uncomplicated childhood epilepsy: a prospective study. II. The EEG as predictor of outcome after withdrawal of treatment.

PURPOSE: We wished to evaluate the prognostic usefulness of various EEG parameters with respect to remission rates after discontinuation of antiepileptic drug (AED) therapy in children treated for epileptic seizures. METHODS: Two hundred forty-four children with uncomplicated epileptic seizures were randomized to either 1 or 3 years of treatment with AEDs. The treatment was then discontinued in patients who had been seizure-free during the last 6 months of their allotted time of treatment (n = 154). After treatment discontinuation, the children were followed for at least 2 years. EEG recordings were performed before treatment was initiated and at regular intervals during treatment. RESULTS: The overall relapse rate was 37%. In many children, the amount of epileptiform activity varied considerably between subsequent recordings made during the treatment. The remission rate was slightly higher for children whose last recordings before AED discontinuation were free of epileptiform activity as compared with children in whom such activity was present. However, children who had irregular generalized spike-wave (SW) activity in the recordings made before discontinuation of treatment had a clearly higher relapse rate (67%) both as compared with children without epileptiform activity (33%) and as compared with children with other types of epileptiform activity (33%) in their last EEG recordings before discontinuation. All children treated for only 1 year whose final EEGs displayed generalized irregular SW activity relapsed. CONCLUSIONS: We conclude that the presence of epileptiform activity does not in itself necessarily influence prognosis after discontinuation of treatment but that certain types of such activity signal a high risk of relapse.

Anticonvulsants↗

Drug interactions with proton pump inhibitors.

Omeprazole, lansoprazole and pantoprazole are all mainly metabolised by the polymorphically expressed cytochrome P450 (CYP) isoform CYP2C19 (S-mephenytoin hydroxylase). All 3 proton pump inhibitors have a very limited potential for drug interactions at the CYP level. Small effects on CYP reported for these compounds are usually of no clinical relevance. No dose related adverse effects have been identified, suggesting that the small proportion of slow metabolisers is at no additional risk for clinically important drug interactions. The absorption of some compounds, e.g. benzylpenicillin (penicillin G), are altered during treatment with proton pump inhibitors as a result of the increased intragastric pH. A synergy has been confirmed between omeprazole and amoxicillin or clarithromycin in the antibacterial effect against Helicobacter pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Topical application of a platelet-activating factor (PAF) antagonist in atopic dermatitis.

Platelet-activating factor (PAF acether) is a lipid mediator with a potent proinflammatory activity. Results derived both from in vitro and in vivo studies suggest a possible role of this substance in the pathophysiology of atopic dermatitis. A double-blind, randomized, multi-center, within-patient study was performed to evaluate the efficacy of a topically applied PAF antagonist (RO-24-0238) in 36 patients with atopic dermatitis. Over a period of 28 days, 0.25 ml of the PAF antagonist and the vehicle (placebo) were applied twice daily on opposite sites of symmetrical lesions (measuring 10 to 20 cm2 each). The overall assessment of the therapeutic efficacy did not demonstrate a superior effect of the PAF antagonist in comparison to placebo, and this was the same with the individual study parameters erythema, scaling, induration and exudation. For reducing pruritus, as assessed by the patient using a visual analogue scale, a statistically significant action was documented during the first 2 weeks of the study (p < 0.04; Wilcoxon rank sum test), with a continued, yet not statistically significant efficacy after weeks 3 and 4. The exact role of the pathological events of atopic dermatitis that might be influenced by a PAF antagonist remains to be determined, but the anti-pruritic component of this substance especially deserves further scientific interest.

Administration, Topical↗