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Biomedical subjects

P Larsson

Publications and source records attributed to P Larsson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Characterisation of human deltoid muscle in patients with impingement syndrome.

Muscle biopsies from the anterior and medial parts of the deltoid of 11 male patients and six male controls were analysed with morphological and immunohistochemical methods. The distribution, area, and capillarization of the muscle fibres were determined, and the amount of connective tissue was measured with staining for type-III collagen. Compared with the controls, the patients with impingement syndrome had more type-I than type-II fibres, but the areas of the different types were almost the same. There was no difference in capillarization per fibre type between patients and controls, but the patients had more connective tissue. The results indicate that patients with impingement syndrome have morphological changes in the deltoid muscle, probably due to immobilisation and pain. They support the hypothesis that the deltoid muscle, the medial part in particular, is affected in patients with impingement syndrome.

Adolescent↗
PubMed1997

Inhibitors of arachidonic acid metabolism reduce DNA and nuclear fragmentation induced by TNF plus cycloheximide in U937 cells.

U937 human myeloid leukemia cells are induced to apoptosis by tumour necrosis factor (TNF) plus cycloheximide (CHX). We have analysed the effect of various inhibitors of the arachidonic acid (AA) metabolism on several features of this process. The formation of high molecular weight and oligonucleosomal DNA fragments as well as nuclear fragmentation were reduced by inhibitors of 5-lipoxygenase (BWA4C and BWB70C), 5-LO activating protein (MK-886), and cytosolic PLA2 (AACOCF3). None of these agents blocked the morphological changes detected by microscopy or flow cytometry, phosphatidylserine exposure on the cell surface or Caspase 3-like activation. AA also induced nuclear fragmentation at a concentration of 1-20 microM. However, the mechanisms by which these inhibitors act, remain unexplained since there was no 5-LO expression in the U937 cells and no AA release followed their stimulation with TNF plus CHX.

Journal Article↗
PubMed1997

Immunization with alum-collagen II complex suppresses the development of collagen-induced arthritis in rats by deviating the immune response.

Collagen-induced arthritis (CIA) is an experimental rat model sharing a number of features with human rheumatoid arthritis (RA). The model is associated with a proinflammatory (TH1) type of immune response and treatments with cytokines associated with TH2 immune responses are beneficial. Since agents with TH1-inducing properties, such as Freund's incomplete adjuvant (FIA), are necessary for disease induction, it is of interest to investigate whether an adjuvant with TH2-inducing properties affects CIA in a different way than does FIA. The authors studied arthritis development in DA rats after immunization with the TH2 stimulatory adjuvant alum adsorbed to rat collagen type II (CII) or collagen II fragments. Such treatments suppressed disease development both prophylactically and therapeutically. This beneficial effect of alum-CII immunization was associated with an increase in the IgG1 anti-CII antibody response as compared to untreated rats or rats pretreated with alum alone. Treatment with alum without the addition of collagen did not have any clinical effect. In addition, alum-CII treated rats had a significantly higher expression of IL-4 mRNA than untreated rats in the lymph nodes, 7 days after CIA induction. The authors suggest that alum-CII induces a TH2 immune response against rat CII which counteracts the development of CIA.

Alum Compounds↗
PubMed1997

Human Lymphocyte Antigen Typing: Direct DNA Typing-The Only Choice?

Exact human lymphocyte antigen (HLA) allele matching and sequence variation are important for matching organ donors, immune response studies, and disease association investigations. The number of HLAs has reached several hundred within each of the different classes. This level of heterogeneity makes routine DNA typing to the allele level problematic using fixed probe and primer technologies. Routine large-batch screening programs where only intermediate-level typing is required can be performed in automated fashion by several DNA technologies. Screening large numbers of samples with probe-based technologies, even oligo array chips, is cost effective. Allele-specific typing is most easily performed using direct sequencing. New sequencing technologies based on cycle sequencing and high-speed capillary gels have made routine sequencing for clinical typing a reality. The complexity of the class I locus requires a detailed analysis of all the polymorphisms within exons 2 and 3. Sequencing strategies are thus designed to use informative variable regions within the flanking introns and the flanking region as well as the untranslated regions. Simliar strategies are being adapted to the complex class II DRB alleles, which now number about 200 different alleles. Greater understanding of HLA diversity and distribution throughout humans and their relatives facilitates organ matching and the history and origins of human populations. Knowledge of parasites and their role in the selection of alleles will ultimately lead to better prediction and manipulation of the immune system response to these organisms. HLA typing is used to determine relative risk to a variety of autoimmune diseases. Future uses of molecular HLA typing may include the prevention and cessation of these self-destructing diseases.

Journal Article↗
PubMed1997

Absorbed dose and image quality in examinations of the colon with digital and analogue techniques.

PURPOSE: Image quality and the absorbed dose to the patient are issues of primary interest in the change-over from the conventional analogue technique to the digital technique in the examination of the colon by means of fluoroscopy. The aim of this study was to compare the incident radiation and to evaluate the image quality in two different X-ray equipment types, one digital and one analogue. MATERIAL AND METHODS: A kerma-area product meter was used to measure the incident radiation to the patient. Both fluoroscopy and total-examination times were measured as was the number of images. An evaluation of image quality was made and statistically analysed. RESULTS AND CONCLUSION: No significant difference in the irradiation dose was observed between the two techniques. The fluoroscopy time was significantly lower with the conventional technique but the total-examination time decreased by 18% with the digital technique. The total number of images taken was higher with the digital technique (25 images compared to 19) owing to the limited field of the image intensifier. Significantly more noise and less sharpness were observed with the digital system but there was no significant difference in contrast or image quality in the various anatomical structures. Although the change-over to the digital system produced a reduction in sharpness and an increase in noise, and no significant dose saving was measured, the digital system was faster to work with and could well be used for diagnostic purposes.

Adult↗
PubMed1997

Binding of 3H-metronidazole in olfactory, respiratory and alimentary epithelia in rats.

Whole-body autoradiography of 3H-metronidazole in rats showed retention of bound metabolites in the epithelia lining the olfactory part of the nose, the tongue, the gingiva, the palate, the pharynx, the oesophagus and the forestomach. In vitro microautoradiography in O2- and N2-atmosphere with some of these tissues indicated reductive formation of bound metabolites in specific cells of the epithelia. Studies with subcellular fractions of the nasal olfactory mucosa showed formation of DNA- and protein-bound metronidazole metabolites. A lower bioactivating capacity was found in experiments with the liver. The bioactivation was dependent on N2-atmosphere, and presence of the P450-inhibitor metyrapone or GSH in the incubation media depressed the protein-binding of metronidazole both in the nasal olfactory mucosa and the liver. These data indicate that the bioactivation is partly P450-dependent and GSH may play an important role in scavaging the bioactivated drug. The epithelial cells with a capacity to bioactivate metronidazole may be potential targets for negative effects of the drug. Whole-body autoradiography also showed a strong binding of radioactivity in the contents of caecum and colon. This can be considered to be due to reductive bioactivation of metronidazole by the intestinal microorganisms and reflects the principal site of action of the drug.

Animals↗
PubMed1997

Expression of phospholipase A2 isoforms in human normal and atherosclerotic arterial wall.

LDL particles must be modified in the arterial wall to be taken up by macrophages at an excessive rate, leading to foam cell formation. Phospholipase A2 (PLA2) has been shown to modify LDL particles in vitro by degrading its phospholipids, resulting in enhanced uptake by macrophages. Reaction products of PLA2 are lysophospholipids and nonesterified fatty acids (mainly arachidonic acid), which are precursors of potent inflammatory mediators and which have been found in atherosclerotic regions of the arterial wall. To elucidate the expression of PLA2 in normal and diseased arteries, frozen tissue sections of human nonatherosclerotic mesenteric artery and carotid plaques were examined by immunohistochemistry using specific antibodies against secretory PLA2 types I and II and cytosolic PLA2 (85 kd). Secretory PLA2 type I was not detected. High expression of secretory PLA2 type II was found throughout the media in both normal and atherosclerotic artery specimens, in which smooth muscle cells dominated. Cytosolic PLA2 was found exclusively in diseased artery, mainly in the intima in regions with an inflammatory infiltrate consisting of macrophages and smooth muscle cells. Furthermore, both normal and atherosclerotic artery possessed substantial PLA2 activity. It is suggested that secretory PLA2 type II could play an important role in early atherogenesis because it is present in the preatherosclerotic arterial wall, where it may lead to LDL modification, foam cell formation, and activation of immune mechanisms.

Arteries↗
PubMed1997

Inhalation of swine dust induces cytokine release in the upper and lower airways.

In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Each subject carried personal samplers for exposure measurements. Inhalable dust and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (> 38 degrees C) in three subjects, and approximately 25% of the subjects experienced symptoms. Bronchial responsiveness to methacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75th percentile)). Following exposure, granulocytes increased more than 50 fold in BAL fluid and more than 40 fold in nasal lavage fluid. IL-1 alpha and IL-1 beta increased significantly in BAL fluid (p < 0.05) and nasal lavage fluid (p < 0.01). IL-6 increased 25 fold in BAL and 15 fold in nasal lavage fluid (p < 0.001). TNF-alpha was below detection limit (0.25 ng.L-1) in most subjects before exposure and increased following exposure to 3.8 (2.4-5.7) and 1.3 (0.6-2.3) ng.L-1 in BAL and nasal lavage fluid, respectively, (p < 0.001). Total inhalable dust was 20.5 (14.6-30.0) mg.m-3 and the concentrations of airborne endotoxin, 3-OH fatty acid and muramic acid were 1.2 (0.8-1.4), 3.5 (2.2-4.5) and 0.9 (0.3-1.9) microgram.m-3, respectively. There was a significant correlation between the IL-6 response in BAL fluid and exposure to dust endotoxin activity and 3-OH fatty acids (p < 0.05). Otherwise, no significant correlations were found between exposure and the cytokine response. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.

Adult↗
PubMed1997

Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency.

Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.

Administration, Inhalation↗
PubMed1997

Loracarbef versus phenoxymethylpenicillin in the treatment of recurrent streptococcal pharyngotonsillitis.

Knowledge of the treatment of recurrent group A streptococcal pharyngotonsillitis has, so far, been based on studies of non-recurrent rather than recurrent episodes of the disease. This multicentre, double-blind, randomized trial was designed to compare the efficacy of loracarbef (200 mg twice daily) vs phenoxymethylpenicillin (penicillin V) (800/1000 mg twice daily) each for 10 days in the treatment of recurrent group A streptococcal pharyngotonsillitis. Among the 331 patients enrolled in the study, 265 were evaluable for efficacy. The combined clinical and bacteriological failure rate was 8.2% in the loracarbef group and 21.5% in the penicillin V group (p = 0.008). Bacterial eradication was noted in 90% of loracarbef-treated patients compared to 66% of penicillin V-treated patients (p < 0.0005). The higher bacteriological eradication and clinical efficacy rate among loracarbef patients might be related to higher stability of loracarbef in the presence of beta-lactamases produced by the oral microflora. These results suggest loracarbef to be a strong candidate for treatment of patients with recurrent group A streptococcal pharyngotonsillitis.

Cephalosporins↗
PubMed1997

Antimicrobial susceptibility testing in Sweden. III. Methodology for susceptibility testing.

A subcommittee of the Swedish Reference Group for Antibiotics, SRGA-M, has worked with standardization of methodology for susceptibility testing. In vitro data obtained with the disk diffusion procedure were collected from 5 clinical laboratories, compiled and presented as histograms of inhibition zones, and compared with data [minimum inhibitory concentrations (MICs) and inhibition zones] obtained from the reference laboratory at the Swedish Institute for Infectious Disease Control on a collection of clinically relevant bacterial species. Results from the reference collection of strains were presented as MIC histograms, and their corresponding inhibition zones were inserted in the compiled zone histograms as identifiable bars. These distributions formed the basis for decisions of breakpoints. Special tests were recommended for the detection of certain resistance mechanisms. A beta-lactamase test should be used for Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and enterococci. Screening for beta-lactam resistance caused by altered penicillin binding proteins should be done by using oxacillin 1 microgram for Streptococcus pneumoniae and Staphylococcus aureus (MRSA), and by phenoxymethylpenicillin 10 micrograms for H, influenzae. The standardized disk diffusion procedure was helpful in detecting enterobacteria carrying beta-lactamases with extended spectra. Registration of inhibition zones will provide a powerful tool for the epidemiological surveillance of antibiotic resistance.

Anti-Bacterial Agents↗
PubMed1996

Cell proliferation in renal cell carcinoma--a comparative study of cell kinetic methods.

Four different methods of assessing cell proliferation in renal cell carcinoma were compared in a total of 136 samples to analyze their degree of agreement and usefulness. The methods compared were flow cytometric S-phase (S-FCM) analysis, proliferating cell nuclear antigen expression detected by immunohistochemistry (PCNA-IHC), in vivo iododeoxyuridine incorporation analyzed with immunohistochemistry (IdUrd-IHC), and flow cytometry (IdUrd-FCM). The mean S-FCM fraction was 5.9%, compared with a mean PCNA-IHC labeling index of 4.7%. The mean labeling indices obtained by IdUrd-IHC and IdUrd-FCM were 1.2% and 1.7%, respectively. The four methods correlated well with each other. When the methods were compared according to Bland and Altman, good agreement was shown. A statistically significant difference in proliferation between diploid and aneuploid tumor samples was found with all methods (P < 0.001). The results showed that the four different methods provided comparable information on proliferative activity, although different cell cycle compartments were monitored.

Aneuploidy↗
PubMed1996

Expression of interferon-gamma (IFN-gamma), IL-10, IL-12 and transforming growth factor-beta (TGF-beta) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA).

The expression of immunoregulatory cytokines was investigated in freshly isolated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with RA, using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN-gamma, TGF-beta, IL-10 and IL-12 (p40) transcripts were detected in SFMC of patients with early disease (<1 year duration) as well as in patients with long standing arthritis (>1 year). The expression of IFN-gamma, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from health control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with levels found in serum from RA patients and control individuals. High levels of TGF-beta mRNA were found in SFMC, but a significantly decreased TGF-beta/beta2-microglobulin (beta2-M) ratio was found compared with PBMC from both patients and control individuals. IL-4mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBMC did not differ from control PBMC, with the exception of a decreased TGF-beta/beta2-M ratio in RA patients with early disease. Our findings of IFN-gamma mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune response. The presence of TGF-beta and IL-10 mRNA indicates that immunosuppressive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immune activation.

Adult↗
PubMed1996

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography.

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life (t1/2 beta) after the intravenous injection was 4.2 +/- 0.5 h, the volume of distribution (Vd(ss) 1.1 +/- 0.2 L/kg and the total body clearance (ClB) 131.2 +/- 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 +/- 16%. The plasma maximum concentration (Cmax) 31.9 +/- 2.3 micrograms/mL was reached 2 h after the oral administration and the oral elimination half-life (t1/2 beta) was 4.7 +/- 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [3H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.

Administration, Oral↗