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Biomedical subjects

P Larsson

Publications and source records attributed to P Larsson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Time course of interleukin-6 and tumor necrosis factor-alpha increase in serum following inhalation of swine dust.

Inhalation of swine dust induces airway inflammation and general symptoms, such as fever and malaise. In the present investigation, the presence and time course of changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum were studied to evaluate possible mechanisms by which inhalation of swine dust induces general symptoms. A group of 14 previously nonexposed subjects weighed swine for 3 h. The average +/- SD inhalable dust concentration was 22.4 +/- 4.7 mg/m3 and endotoxin, 1.2 +/- 0.4 microgram/m3. TNF-alpha in serum increased from 2.5 (1.8 to 3.1) ng/L (median, interquartile range) before exposure to maximum values 10.0 (4.6 to 15.7) ng/L between 3 and 5 h after the start of exposure. IL-6 increased from less than 1.5 to 21.4 (18.6 to 33.6) ng/L 4 to 11 h after the start of exposure. Maximum IL-6 occurred 1 to 5 h after the maximum TNF-alpha. In many subjects, however, an early rise in IL-6 parallel to the change in TNF-alpha was seen. The results that some of the peripheral reactions to swine dust might be mediated by TNF-alpha and IL-6. The early rise in IL-6 implies multiple origins of the IL-6.

Adult↗
PubMed1996

Assessment of the relative systemic potency of inhaled fluticasone and budesonide.

Studies using dry powder devices have suggested that fluticasone propionate (FP) has a greater systemic effect than budesonide (BUD). The aim of the present study was to investigate and compare the relative systemic potency of FP and BUD from their respective pressurized metered-dose inhalers (pMDIs). A placebo-controlled, open, randomized, cross-over study was conducted in 21 healthy male volunteers. Placebo, BUD (200, 400 and 1,000 micrograms b.i.d.) and FP (200, 375 and 1,000 micrograms b.i.d.) were inhaled for 4 days, with a wash-out period of at least 3 days between treatments. Blood samples for cortisol analysis were drawn during the last 24 h of each treatment period. Cortisol levels, measured as 24 h pooled plasma cortisol, were statistically significantly lower (p = 0.0001) for all dose levels during FP pMDI treatment (21, 39 and 84% suppression from placebo) than during BUD pMDI treatment (1, 3 and 27% suppression from placebo). The relative systemic potency FP:BUD was 3.7:1 (95% confidence interval (95% CI) 2.9-4.8)). The relative systemic potency based on the single 08:00 h samples was 5.2:1 (95% CI 3.0-9.3). In conclusion, in healthy male volunteers using pressurized metered-dose inhalers, fluticasone propionate was shown to have a stronger systemic effect than budesonide.

Administration, Inhalation↗
PubMed1996

Bioactivation of aflatoxin B1 in the nasal and tracheal mucosa in swine.

Whole-body autoradiography of 3H-labeled aflatoxin B1 in young pigs showed a localization of bound label in the nasal olfactory and respiratory mucosa, in the tracheo-laryngeal mucosa, and in the conjunctiva, in addition to the liver. Whole-body and microautoradiography also showed a labeling of pigmented tissues, which can be ascribed to a melanin binding of AFB1. In vitro experiments with microsomal preparations of various tissues from sows revealed that the nasal respiratory and olfactory mucosa had the highest capacity to form DNA-bound aflatoxin B1-metabolites. The tracheal mucosa and the liver, in order, had lesser binding capacity. The lung was found to be devoid of aflatoxin B1-bioactivating capacity. In vitro microautoradiography revealed bound label in specific cell types in the nose and trachea and in some cells of the conjunctiva. A drastic decrease in the aflatoxin B1-DNA binding was observed when microsomal preparations of the nasal respiratory and olfactory mucosa were incubated in the presence of reduced glutathione, but without any addition of cytosolic glutathione-S-transferases. In incubations of liver microsomes under these conditions a somewhat lower inhibition of the aflatoxin B1-DNA binding was seen. Our results demonstrate that the nasal olfactory and respiratory mucosa and the tracheal mucosa have a higher capacity than the liver to bioactivate aflatoxin B1 in swine. Our data further show that microsomal-associated glutathione-S-transferases with a high capacity to catalyze the conjugation of the reactive aflatoxin B1-epoxide to reduced glutathione are present in the nasal olfactory and respiratory mucosa of swine.

Aflatoxin B1↗
PubMed1996

"Corynebacterium aquaticum" wound infection after high-pressure water injection into the foot.

The organisms presently named "Corynebacterium aquaticum" have their natural habitat in water and are increasingly often isolated in clinical specimens, but are very seldom the proven cause of infection. A case of a 24-year-old man with a "C aquaticum" wound infection secondary to a high-pressure water injection injury in the foot is described. Cefadroxil and cefuroxime were used for treatment.

Adult↗
PubMed1996

Proliferating cell nuclear antigen expression in renal cell carcinoma. Prognostic implications.

The proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with cells in active cell cycle. The expression of PCNA was evaluated immunohistochemically in 3-6 samples from 68 renal cell carcinomas. A total of 279 tumour samples were analysed using the monoclonal antibody PC-10, and the percentage of positively stained cell nuclei (PCNA-index) was determined. The tumour PCNA-index varied between 0.9-17.5%, with a mean value of 4.9%, significantly different from normal kidney cortex samples (p < 0.001). A significant difference in PCNA-index was found between the different tumour grades, whereas no significant difference was found between clinical stages. Concerning DNA ploidy, aneuploid tumours had a significantly higher PCNA-index compared with diploid tumours (p = 0.002). There was a significant survival advantage for patients with low tumour PCNA-indices (< 3.5%) compared with those with high indices (> 3.5%, p = 0.019), a difference also found for patients with non-metastatic disease (p = 0.012). Our data shows that PCNA expression can be analysed and that it may constitute an additional prognostic parameter for patients with renal cell carcinoma.

Adult↗
PubMed1995

Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes.

Stimulated B-lymphocytes, isolated from patients with chronic lymphocytic leukemia of B-cell type (B-CLL cells) or from human tonsils, produced similar amounts of leukotriene (LT) B4 and 5-hydroxyeicosatetraenoic acid (5-HETE) as polymorphonuclear granulocytes. Unlike intact granulocytes or monocytes, human B-lymphocytes require calcium ionophore, exogenous arachidonic acid and an oxidative environment in order to produce 5-lipoxygenase products. Several thiol-reactive compounds such as N-ethylmaleimide, methyl methanethiosulfonate, azodicarboxylic acid bis[dimethylamide] (diamide) as well as hydrogen peroxide were all found to stimulate cellular leukotriene biosynthesis. Reverse transcriptase (RT)-PCR analysis demonstrated the expression of 5-lipoxygenase, 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase mRNA in B-CLL cells. Western blot analysis demonstrated a band corresponding to the molecular size of FLAP in the B-CLL cell membrane. Furthermore, MK886, the FLAP-binding cellular leukotriene biosynthesis inhibitor, reduced both LTB4 and 5-HETE formation. Immunocytochemistry showed that 5-lipoxygenase was mainly localized in the nuclei of non-activated B-CLL cells, tonsillar B-lymphocytes and monoclonal B-cells. In contrast, neither human peripheral T-lymphocytes nor Jurkat cells were stained. These results suggest that 5-lipoxygenase and its products function in the nucleus of B-lymphocytes.

5-Lipoxygenase-Activating Proteins↗
PubMed1995

Mechanical versus biological valve prosthesis: a ten-year comparison regarding function and quality of life.

To determine the long-term outcome of biological and mechanical heart valve prostheses, we compared the Biocor, a new generation of porcine bioprosthesis, with the St. Jude Medical mechanical prosthesis. One hundred consecutive patients operated on between 1983 and 1985 with the Biocor in the aortic, mitral, or both positions (without concomitant cardiac procedures) were followed until January 1993, together with 100 matched patients implanted with the St. Jude valve. The mean age was 66 and 67 years, respectively. The follow-up was 100% complete. Valve-related mortality differed significantly, with a freedom rate of 80.7% +/- 9.0% for the St. Jude group and 97.7% +/- 1.6% for the Biocor group. There were few thromboembolic events, with no significant difference between the groups. Anticoagulant-related hemorrhage occurred almost exclusively in the St. Jude group (2.3%/patient-year), and reoperations were required almost exclusively in the Biocor group (1.8%/patient-year). The occurrence of all valve-related complications (mortality plus morbidity) differed markedly, with an actuarial freedom at 10 years of 55.8% +/- 9.8% for St. Jude and 80.0% +/- 4.4% for the Biocor. Quality of life and echocardiographic measurements did not differ significantly between the groups. We conclude from this study that the long-term performance of the Biocor and St. Jude are comparable, even though valve-related complications tended to be fewer in the Biocor group, with a significantly lower incidence of valve-related death.

Actuarial Analysis↗
PubMed1995

Extrahepatic bioactivation of aflatoxin B1 in fetal, infant and adult rats.

Whole-body autoradiography of 3H-labelled aflatoxin B1 (3H-AFB1) in female non-pregnant adult and infant Sprague-Dawley rats showed retention of tissue-bound radioactivity, in addition to the liver, in the mucosa and some glands in the nose, and in the mucosa of the nasopharynx, trachea, bronchioles, colon and caecum. The extrahepatic binding was most pronounced in the infant rats. In a rat pretreated with the glutathione (GSH)-depleting agent phorone, bound labelling was also seen in the superficial part of the mucosa of the glandular stomach. Autoradiography of 3H-AFB1 in pregnant rats showed a marked localization of bound AFB1-metabolites in the fetal nasal olfactory and tracheal mucosa. In vitro experiments demonstrated that the nasal olfactory mucosa had a much higher capacity than the liver to form AFB1-metabolites which bound to DNA and protein. The bioactivation was observed both pre- and post-natally and increased with age. Bioactivation was found also in the caecum, the colon and the lateral nasal gland (Steno's gland), but not in the small intestine, oesophagus or Harderian gland. Our results indicated that glutathione-S transferase activity catalysing the AFB1-8,9-epoxide GSH-conjugation was present in the nasal olfactory mucosa and liver at all pre- and post-natal ages examined. Several of the extrahepatic tissues able to bioactivate AFB1 have been reported to be targets for the carcinogenicity of the substance. Our results indicate that the extrahepatic carcinogenicity of AFB1 is correlated to a local bioactivation in the sensitive tissues.

Aflatoxin B1↗
PubMed1995

Intravenous enterostatin does not affect single meal food intake in man.

Enterostatin, a pentapeptide released with colipase from pancreatic procolipase in man, affects eating behaviour in animals. We report the first phase II study of intravenous (i.v.) enterostatin (D3800) in obese but otherwise healthy men. Eighteen men (mean age 37 years, mean body mass index 34.9 kg/m2) completed a double-blind, randomized, crossover placebo controlled trial. After in initial session, each man received i.v. 4 mg D3800, 16 mg D3800 or placebo in random order over three sessions, immediately before a test meal served on a universal eating monitor. No statistically significant effect of i.v. enterostatin on any uptake or rating variable was observed. Several factors may explain the lack of effect, e.g. the inability of i.v. enterostatin to reach a site of action, the time between i.v. administration and eating, and the possibility that the only human responders are those who express particular fat preferences.

Adult↗
PubMed1995

Diverse expression of cytosolic phospholipase A2, 5-lipoxygenase and prostaglandin H synthase 2 in acute pre-B-lymphocytic leukaemia cells.

Several lines of evidence suggest that phospholipases A2, leukotrienes and prostaglandins play a role in the proliferation of haemopoietic cells. The expression of genes involved in the biosynthesis of leukotrienes and prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight patients with acute pre-B-lymphocytic leukaemia (pre B-ALL). RT-PCR analysis demonstrated that four of the investigated pre-B-ALL clones expressed the gene coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5-lipoxygenase. In contrast, the remaining four pre-B-ALL clones expressed 5-lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of these two genes are different and that their cellular functions are not linked to each other. The capacity of pre B-ALL cells to produce LTB4 and to express the 5-lipoxygenase protein, correlated with the expression of 5-lipoxygenase mRNA. All pre-B-ALL clones expressed genes coding for 5-lipoxygenase activating protein (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the eight pre B-ALL clones expressed PGH synthase 2. In comparison, normal tonsillar B cells did not express cPLA2 or PGH synthase 2.

5-Lipoxygenase-Activating Proteins↗
PubMed1995

Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid.

BACKGROUND: Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. METHODS: Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush. RESULTS: Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis. CONCLUSIONS: Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.

Adult↗
PubMed1995

Similar quality of life after heart valve replacement with mechanical or bioprosthetic valves.

The goal of this study was to determine if there was a difference in the quality of life (QoL) between patients receiving bioprosthetic (Biocor, BIO) or mechanical (St. Jude Medical, SJM) valve prosthesis. In January 1993 we assessed the psychological outcome of heart valve surgery among 183 (87 BIO, 96 SJM) of 220 survivors in a selected and matched cohort of 140 BIO and 140 SJM recipients who had their valve replacement between 1983 and 1989. The BIO and SJM groups were equal in terms of mean age, gender, valve position, educational level, marital status and follow up time. Questions concerning QoL, in terms of coping capacity, social support, and general emotional status as well as emotions concerning valve-related complications, were answered by the patients marking a non-graded visual analogous scale, ranging from total agreement to total disagreement. We found no significant difference between patients receiving BIO and those receiving SJM prostheses regarding coping capacity (62 +/- 2 vs. 65 +/- 2), social support (77 +/- 3 vs. 76 +/- 2), or emotional status (63 +/- 3 vs. 65 +/- 3). When subdividing patients by age below and above 60 years, gender, functional class, valve position and complication, we found several significant differences, but the two prosthetic groups were largely similar. Females had a significantly lower level of coping capacity and emotional status than males. Coping capacity and emotional status were significantly correlated with functional class, while social support was not. Coping capacity tended to be lower among patients who had experienced complications and this was more pronounced with BIO.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1994

Cell kinetics of renal cell carcinoma studied with in vivo iododeoxyuridine incorporation and flow cytometry.

In 29 patients with renal cell carcinoma tumor cell kinetics were studied by in vivo labeling with 100 mg. iododeoxyuridine given 3 to 7 hours before nephrectomy. Two to 6 samples were analyzed from each tumor after fixation in ethanol. Iododeoxyuridine was analyzed by specific antibodies using flow cytometric analysis of labeled cells and parameters, such as labeling index and potential tumor doubling time, could be determined. Samples from 28 tumors were evaluable. Mean labeling index of the tumors was 2.7%, which was significantly different from the 0.35% index in kidney cortex tissue. There was no statistical difference in labeling index among the clinical stages. The mean potential tumor doubling time in the tumor cells was 20.3 days, which was significantly different compared with 137.7 days in kidney cortex tissue. There was a frequent intra-tumoral heterogeneity of potential tumor doubling times. Diploid and aneuploid samples had significantly different potential tumor doubling (mean 37.4 and 12.5 days, respectively). Potential tumor doubling had a significant impact on the survival time (p = 0.004), which also was noted in the patients with aneuploid tumors (p = 0.003). Our study shows that in vivo incorporation of iododeoxyuridine successfully can be analyzed in renal cell carcinoma. Potential tumor doubling time gives valuable prognostic information on the clinical behavior of the patients.

Adult↗
PubMed1994

Hepatic and extrahepatic bioactivation and GSH conjugation of aflatoxin B1 in sheep.

Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiva. Microautoradiography revealed that the bound material was confined to specific cell types in extrahepatic tissues. Whole-body autoradiography also showed a labelling of pigmented tissues (such as the eye melanin), which can be ascribed to a melanin affinity of AFB1. In vivo experiments, performed with microsomal preparations of tissues from ewe and lamb showed that several of the extrahepatic tissues were more efficient than the liver in forming DNA-bound AFB1 metabolites. The nasal olfactory mucosa was by far the most effective tissue in this respect. AFB1 induced a high number of gene mutations in Salmonella typhimurium TA100 when incubated with supernatant preparations (9000 g) of the nasal olfactory mucosa, whereas incubations with preparations of the liver resulted in a lower effect. It has been reported that AFB1 can induce nasal tumours in sheep. When microsomal preparations of various tissues were incubated in the presence of reduced glutathione (GSH), but without any addition of cytosolic glutathione-S-transferase (GST), a drastic decrease in the AFB1-DNA binding was seen. Analyses of the water-soluble metabolites formed in the microsomal incubations supplemented with GSH showed fluorescent and ninhydrin-positive metabolites that were not present in the absence of GSH. These results indicate that sheep tissues have intrinsic microsomal GST or cytosolic GSTs associated with the microsomal fraction with a high capacity to catalyse the conjugation of bioactivated AFB1 to GSH. The results of the present study show that several extrahepatic tissues of sheep have a potent capacity to bioactivate AFB1 and also a high capacity to GSH conjugate the bioactivated AFB1.

Aflatoxin B1↗
PubMed1994

A prospective cohort study on breast-feeding and otitis media in Swedish infants.

This study analyzed the effect of breast-feeding on the frequency of acute otitis media. The protocol was designed to examine each child at 2, 6 and 10 months of age. At each visit nasopharyngeal cultures were obtained, the feeding pattern was recorded and the acute otitis media (AOM) episodes were documented. The analysis was based on 400 children from whom complete information was obtained. They represented 83% of the newborns in the study areas. By 1 year of age 85 (21%) children had experienced 111 AOM episodes; 63 (16%) had 1 and 22 (6%) had 2 or more episodes. The AOM frequency was significantly lower in the breast-fed than in the non-breast-fed children in each age group (P < 0.05). The first AOM episode occurred significantly earlier in children who were weaned before 6 months of age than in the remaining groups. The frequency of nasopharyngeal cultures positive for Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was significantly higher in children with AOM. At 4 to 7 and 8 to 12 months of age, the AOM frequency was significantly higher in children with day-care contact and siblings (P < 0.05 and < 0.01, respectively). The frequency of upper respiratory tract infections was increased in children with AOM but significantly reduced in the breast-fed group.

Acute Disease↗
PubMed1994

The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy?

Chronic bronchitis is common among smokers, often together with recurrent infectious exacerbations. Streptococcus pneumoniae and Haemophilus influenzae are the pathogens traditionally considered most important. N-acetylcysteine (NAC) treatment has been shown to reduce the number of infectious exacerbations in patients with chronic bronchitis. The mechanism behind this is unknown. We attempted to characterize the intrabronchial bacterial flora in patients with chronic bronchitis in an infection-free interval, and to determine whether pharmacological and immunological factors effected the bacterial occurrence. Twenty two smokers with non-obstructive chronic bronchitis, 19 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD) and 14 healthy nonsmokers underwent bronchoscopy. To obtain uncontaminated intrabronchial samples, a protected specimen brush was used. Quantitative bacterial cultures and virus isolations were performed. Significantly positive bacterial cultures (> 1,000 colony-forming units (cfu).ml-1) were found only in the patients. S. pneumoniae and H. influenzae were found in five patients, and only in the patients without NAC treatment. The most common bacterium was alpha-haemolytic streptococcus. Negative cultures were more common in the healthy controls. Of the various factors examined, only NAC medication had an influence on bacterial numbers. Significantly fewer patients with NAC medication had positive cultures (3 out of 16) than in the group of patients without NAC therapy (15 out of 21). Our results confirm that chronic bronchitis in smokers leads to increased intrabronchial bacterial colonization. We could also confirm that 1,000 cfu.ml-1 is an adequate cut-off level for significant bacterial growth when using the protected specimen brush. NAC medication was associated with low bacterial numbers.

Acetylcysteine↗