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Biomedical subjects

S Persson

Publications and source records attributed to S Persson.

At least 37 records · Page 2Linked to original sources

[Results of a primary health care study on alcohol: 17 per cent of men, 8 per cent of women were probable heavy consumers].

A questionnaire study designed to elicit an impression of the proportion of heavy drinkers among primary care patients, carried out at five primary facilities in Västerbotten County, showed 12 per cent of the patients (17% of the men, 8% of the women) to be probable heavy alcohol consumers. This emphasises the strategically advantageous position of primary care facilities with a view to early intervention. Age was found to be a significant determinant of alcohol consumption, but not place of residence or the reason for consulting.

Adult↗

Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells.

Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.

3T3 Cells↗

Molecular ordering of interfacially localized tryptophan analogs in ester- and ether-lipid bilayers studied by 2H-NMR.

Perdeuterated indole-d6 and N-methylated indole-d6 were solubilized in lamellar liquid crystalline phases composed of either 1,2-diacyl-glycero-3-phosphocholine (14:0)/water or 1,2-dialkyl-glycero-3-phosphocholine(14:0/water. The molecular ordering of the tryptophan analogs was determined from deuteron quadrupole splittings observed in 2H-NMR spectra on macroscopically aligned lipid bilayers. NMR spectra were recorded with the bilayers oriented perpendicular to or parallel with the external magnetic field, and the values of the splittings differed by a factor of 2 between these distinct orientations, indicating fast rotational motion of the molecules about an axis parallel to the bilayer normal. In all cases the splittings were found to decrease with increasing temperature. Relatively large splittings were observed in all systems, demonstrating that the tryptophans partition into a highly anisotropic environment. Solubilization most likely occurs at the lipid/water interface, as indicated by 1H-NMR chemical shift studies. The 2H-NMR spectra obtained for each analog were found to be rather similar in ester and ether lipids, but with smaller splittings in the ether lipid under similar conditions. The difference was slightly less for the indole molecule. Furthermore, in both lipid systems the positions of the splittings from indole were different from those of N-methyl indole. The results suggest that 1) the tryptophan analogs are solubilized in the interfacial region of the lipid bilayer, 2) the behavior may be modulated by hydrogen bonding in the case of indole, and 3) hydrogen bonding with the lipid carbonyl groups is not likely to play a major role in the solubilization of single indole molecules in the ester lipid bilayer interface.

Biophysical Phenomena↗

Microbiologic analysis of teeth with failed endodontic treatment and the outcome of conservative re-treatment.

OBJECTIVE: The purposes of this study were to determine what microbial flora were present in teeth after failed root canal therapy and to establish the outcome of conservative re-treatment. STUDY DESIGN: Fifty-four root-filled teeth with persisting periapical lesions were selected for re-treatment. After removal of the root filling, canals were sampled by means of advanced microbiologic techniques. The teeth were then re-treated and followed for up to 5 years. RESULTS: The microbial flora was mainly single species of predominantly gram-positive organisms. The isolates most commonly recovered were bacteria of the species Enterococcus faecalis. The overall success rate of re-treatment was 74%. CONCLUSIONS: The microbial flora in canals after failed endodontic therapy differed markedly from the flora in untreated teeth. Infection at the time of root filling and size of the periapical lesion were factors that had a negative influence on the prognosis. Three of four endodontic failures were successfully managed by re-treatment.

Dental Pulp Cavity↗

Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: Results of a 20-year median follow-up.

From May 1975 until May 1980,128 operable breast cancer patients, clinical stage I-II, had a core bone marrow biopsy (BMB) from the posterior iliac crest as a part of the routine diagnostic work-up at the time of initial diagnosis. The mean age of the patients was 56 years, range 26-93. In a previous study on this material, 10 patients (7.8 per cent) were positive for tumor cells and 118 negative by conventional histopathology of BMB [1]. In 1996 we reexamined all BMB separately at two laboratories, using monoclonal antibodies against cytokeratins AE1-AE3, KL1, CAM 5-2 (DOP), and DC10, BA17 (MCI). The number of extrinsic cells in the bone marrow was graded positive for micrometastases when > or = 5 cells or suspicious when 1-4 cells per approximately 2 x 10(6) bone marrow cells were found, using high power field magnification. Micrometastases were detected in 17 patients (13.3 per cent) and another 8 patients were classified as suspicious. The presence of micrometastases was correlated to the axillary lymph node stage and primary tumor location. Median follow-up was 20 years. All 17 micrometastatic patients relapsed and died within 6 years of disease progression with evident osseous metastases. There was one disease-free survivor of the 8 patients with suspicious BMB after 17 years of follow-up. The median overall survival was significantly shorter in tumor-cell positive patients, being 1.9 years compared to 11.7 years in the BMB negative and BMB suspicious groups (p < 0.0001). Immunohistochemical analysis of core BMB taken postoperatively may be useful in predicting the prognosis in patients with breast cancer clinical stage I-II.

Adult↗

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization.

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.

Adult↗

Influence of membrane-spanning alpha-helical peptides on the phase behavior of the dioleoylphosphatidylcholine/water system.

The effect of solubilized hydrophobic peptides on the phase behavior of dioleoylphosphatidylcholine (DOPC)/water system was studied by 2H- and 31P-NMR spectroscopy and by x-ray diffraction, and partial phase diagrams were constructed. The utilized peptides were HCO-AWW(LA)5WWA-NHCH2CH2OH (WALP16), which is an artificial peptide designed to resemble a transmembrane part of a membrane protein; and VEYAGIALFFVAAVLTLWSMLQYLSAAR (Pgs peptide E), a peptide that is identical to one of the putative transmembrane segments of the membrane-associated protein phosphatidylglycerophosphate synthase (Pgs) in Escherichia coli. Circular dichroism spectroscopy suggests that both peptides are mostly alpha-helical in DOPC vesicles. The most striking features in the phase diagram of the WALP16/DOPC/water system are 1) a single lamellar liquid crystalline (L alpha) phase forms only at very low peptide concentrations. 2) At low water content and above a peptide/lipid molar ratio of approximately 1:75 a reversed hexagonal liquid crystalline (H[II]) phase coexists with an L alpha phase, while in excess water this phase forms at a peptide/lipid molar ratio of approximately 1:25. 3) At peptide/lipid ratios > or =1:6 a single H(II) phase is stable. Also, the Pgs peptide E strongly affects the phase behavior, and a single L alpha phase is only found at low peptide concentrations (peptide/lipid molar ratios <1:50), and water concentrations <45% (w/w). Higher peptide content results in coexistence of L alpha and isotropic phases. Generally, the fraction of the isotropic phase increases with increasing temperature and water concentration, and at 80% (w/w) water content only a single isotropic phase is stable at 55 degrees C. Thus, both peptides were found to be able to induce nonlamellar phases, although different in structure, in the DOPC/water system. The phase transitions, the extensions of the one-phase regions, and the phase structures observed for the two systems are discussed in terms of the molecular structure of the two peptides and the matching between the hydrophobic lengths of the peptides and the bilayer thickness of DOPC.

Amino Acid Sequence↗

Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis.

This study investigated the role of infection on the prognosis of endodontic therapy by following-up teeth that had had their canals cleaned and obturated during a single appointment. The root canals of 55 single-rooted teeth with apical periodontitis were thoroughly instrumented and irrigated with sodium hypochlorite solution. Using advanced anaerobic bacteriological techniques, post-instrumentation samples were taken and the teeth were then root-filled during the same appointment. All teeth were initially infected; after instrumentation low numbers of bacteria were detected in 22 of 55 root canals. Periapical healing was followed-up for 5 years. Complete periapical healing occurred in 94% of cases that yielded a negative culture. Where the samples were positive prior to root filling, the success rate of treatment was just 68%--a statistically significant difference. Further investigation of three failures revealed the presence of Actinomyces species in each case; no other specific bacteria were implicated in failure cases. These findings emphasize the importance of completely eliminating bacteria from the root canal system before obturation. This objective cannot be reliably achieved in a one-visit treatment because it is not possible to eradicate all infection from the root canal without the support of an inter-appointment antimicrobial dressing.

Bacteria↗

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49.

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.

Adult↗

Incidence of awareness in total i.v. anaesthesia based on propofol, alfentanil and neuromuscular blockade.

BACKGROUND: There is no reliable technique for monitoring drug concentrations in total i.v. anaesthesia (TIVA) with muscle relaxation. An increased risk of awareness with TIVA has been stated as a possible drawback. The present study was conducted in order to assess the incidence of conscious awareness in TIVA based on propofol, alfentanil and neuromuscular blockade. METHODS: One thousand patients anaesthetized with TIVA based on propofol, alfentanil, and neuromuscular blockade were subjected postoperatively to a structured interview for conscious awareness on two separate occasions: on discharge from the post-anaesthesia care unit, and the day after anaesthesia. Five hundred of these patients were also interviewed a third time, approximately 1 week later. RESULTS: Two cases of awareness were detected (0.2%). One of these was identified immediately after extubation. The second patient had no memory of intraoperative events or dreams at the first interview, recalled a bad dream on the day after, and had explicit recall of intraoperative events at the interview 8 days later. In both cases, haemodynamic signs of inadequate anaesthesia were present. The incidence of conscious awareness in this study is similar to the lowest previously reported incidence of awareness following general anaesthesia in patients who had been paralyzed and thereafter subjected to a structured postanesthesia interview. CONCLUSIONS: If the true incidence of conscious awareness is to be determined, interviews must be extended beyond the first postoperative day. Our study indicates that if appropriate dosing of propofol and alfentanil are adhered to, and proper action is taken in case of haemodynamic alterations suggestive of inadequate anaesthesia, the incidence of conscious awareness in non-cardiac TIVA with neuromuscular blockade is low.

Adolescent↗

Association between pre-PTCA blood haemoglobin concentration and the risk of symptomatic restenosis after successful PTCA of primary coronary stenoses.

BACKGROUND: Thrombus formation at the dilation site has been suggested to initiate the restenosis process after percutaneous transluminal coronary angioplasty (PTCA). High haemoglobin concentrations may predispose to thrombus formation by increasing blood viscosity, slowing coronary blood flow and increasing thrombocyte adhesion. METHODS: Pre-PTCA blood haemoglobin concentrations (Hb) in 44 patients with symptomatic restenosis > or = 50% of the vessel diameter (Group A) were compared with Hb in the remaining 215 patients in a consecutive study population (Group B). RESULTS: Median Hb (range) was 149 (119-164) g/l in Group A and 142 (117-164) g/l in Group B, P = 0.004. Odds ratio (95% CI) for symptomatic restenosis was 3.22 (1.62-6.42) when Hb was dichotomised according to the median in the entire material. Hb, but not sex was a significant risk factor in multivariate analysis. CONCLUSION: Hb is a hitherto not recognized factor associated with the risk of symptomatic restenosis after PTCA and may be a link coupling male sex with increased risk of restenosis.

Adult↗

New aspects on membrane lipid regulation in Acholeplasma laidlawii A and phase equilibria of monoacyldiglucosyldiacylglycerol.

A new membrane lipid, monoacyldiglucosyldiacylglycerol (MADGlcDAG), was recently discovered in Acholeplasma laidlawii strain A-EF22, demanding a new study of the biosynthetic regulation, and the phase behavior, of the glucolipids in this organism. The only liquid-crystalline phase formed by MADGlcDAG is a reversed hexagonal phase. A. laidlawii A-EF22 synthesizes four lipids that have the ability to induce the formation of reversed nonlamellar phases: MADGlcDAG, monoglucosyldiacylglycerol (MGlcDAG), monoacylmonoglucosyldiacylglycerol (MAMGlcDAG), and diacylglycerol (DAG). A Cn value of approximately 16 seems to be a critical value for the fractions of these lipids in the membrane: the fractions of MADGlcDAG and MGlcDAG are largest when the Cn values are lower than 16, while the fractions of MAMGlcDAG and DAG are largest when the Cn values are higher than 16. The fraction of nonlamellar-forming lipids was 55 mol% when the Cn value was 14.8 and the degree of unsaturation was 33 mol%. This fraction was reduced to 7 mol% when the Cn value and the degree of unsaturation were increased to 17.8 and 92 mol%, respectively, i.e., at conditions that markedly favor the formation of reversed nonlamellar phases. These observations convincingly show that a balance between lamellar- and nonlamellar-forming lipids is maintained in the membrane and strongly support the validity of the lipid regulation model proposed by us. From earlier biochemical data, obtained with short acyl chains, that were difficult to reconcile with our regulation model, it could be predicted that a lipid ought to be synthesized that assists MGlcDAG to maintain the nonlamellar-forming properties with the short chains. It is shown in the present work that this lipid is MADGlcDAG and that the regulation of the balance between lamellar- and nonlamellar-forming lipids is even more complex and sophisticated in A. laidlawii A-EF22 than previously proposed.

Acholeplasma laidlawii↗

Changes in early and late diastolic filling patterns induced by long-term adrenergic beta-blockade in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: beta-Blockers have been used in patients with idiopathic dilated cardiomyopathy to improve cardiac performance and theoretically would be beneficial to diastolic function. However, there are few reports on changes in diastolic function during chronic pharmacological treatment of congestive heart failure. METHODS AND RESULTS: The present study was a substudy in the international Metoprolol in Dilated Cardiomyopathy Trial. Transmitral Doppler echocardiography was used to evaluate diastolic function in 77 patients randomly assigned to placebo (n = 37) or metoprolol (n = 40). The patients were treated for 12 months. Changes in Doppler flow variables in the metoprolol group implied a less restrictive filling pattern, expressed as an increase in E-wave deceleration time (placebo, 185 +/- 126 to 181 +/- 64 ms; metoprolol, 152 +/- 63 to 216 +/- 78 ms; P = .01, placebo versus metoprolol). Maximal increase in deceleration time had occurred by 3 months, whereas systolic recovery was achieved gradually and maximal effect was seen by 12 months of treatment. Although deceleration time was correlated to heart rate at baseline, changes in deceleration time were not significantly correlated to changes in heart rate during treatment. CONCLUSIONS: During the first 3 months of treatment, maximal effects on diastolic variables were reached, whereas the most prominent effect on systolic function was seen late in the study. It is suggested that effects on diastolic filling account for subsequent later myocardial systolic recovery. The E-wave deceleration time, which in recent studies has been shown to be a powerful predictor of survival, was significantly improved in the metoprolol-treated patients.

Adrenergic beta-Antagonists↗

Interleukin-10 suppresses the development of collagen type II-induced arthritis and ameliorates sustained arthritis in rats.

The collagen-induced arthritis model in DA rats induced with homologous rat type II collagen was chosen to determine the therapeutic capacity and effects on autoimmunity by IL-10. Systemic IL-10 treatment (100 or 10 micrograms/day) with mini-osmotic pumps during the periods of arthritis onset (days 12-20 after immunization) decreased the frequency of arthritis and delayed the onset and reduced the severity of arthritis in the few rats that eventually developed arthritis. Concomitantly, levels of autoantibodies to CII were reduced. To test the activity on established arthritis, IL-10 was administered subcutaneously in the paws. This treatment reduced the swelling but did not block the arthritis process. The effective treatment required 100 micrograms of IL-10 every 12th hour while 50 micrograms of IL-10 had little effect, although a tendency of reduced paw swelling was observed. Surprisingly, therapeutic IL-10 treatment led to higher serum levels of autoantibodies to CII. The highest doses of IL-10 (100 micrograms) did not show any apparent toxic effects when given locally or systematically. Taken together, this study suggests that IL-10 is a candidate for treatment of rheumatoid arthritis.

Animals↗

Heparan sulphate/heparin glycosaminoglycans with strong affinity for the growth-promoter spermine have high antiproliferative activity.

Depletion of intracellular polyamine pools inhibits cell proliferation. Polyamine pools are maintained by intracellular synthesis and by uptake from the extracellular environment. It may be expected that cationic polyamines are sequestered by the polyanionic glycosaminoglycan substituents of extracellular proteoglycans. Moreover, highly sulphated heparin-related glycans inhibit growth of human embryonic lung fibroblasts. We have therefore investigated interactions between polyamines and heparin-related glycosaminoglycans. Affinity chromatography of various polyamines on heparin-agarose indicated that spermine was the only polyamine that bound efficiently to this type of glycan. By using equilibrium dialysis we found that spermine binds to a highly sulphated heparan sulphate/heparin preparation with a dissociation constant of 3.7 x 10(-5)M. Enzymatic degradation of heparan sulphate using three different heparan sulphate/heparin lyases, separately or in combination and in the absence or presence of spermine, was used to generate spermine-binding and degradation-protected oligosaccharides. As indicated by chromatographic and electrophoretic analysis a size- and chargeheterogeneous collection was obtained. However, protected oligosaccharides derived from antiproliferative heparan sulphates were inactive. Highly sulphated, antiproliferative heparan sulphates were subfractionated on spermine-agarose yielding high-affinity material with increased antiproliferative activity. A very potent material was obtained from pig skin. Although there was generally a clear correlation between high spermine-affinity and strong growth-inhibition, no correlation with sulphate content or oligosaccharide mapping patterns could be detected. Beef lung heparan sulphate comprised naturally occurring fragments of eicosasaccharide size with substantially increased specific activity. As these fragments were longer than oligosaccharides generated by enzymatic degradation in the presence of spermine (hexa- to tetradecasaccharide), multiple spermine-binding sites in tandem may be necessary to induce antiproliferative activity.

Animals↗

Update on the use of angiotensin converting enzyme inhibitors and calcium antagonists in postinfarction patients.

AIM: To review the results of recent studies on the use of angiotensin converting enzyme (ACE) inhibitors and calcium antagonists in patients after an acute myocardial infarction. METHOD: Literature review. CONCLUSIONS: ACE inhibition reduces mortality and morbidity and improves quality of life in a cost-effective way, demonstrating increased benefits with increasing risks. Calcium antagonism with verapamil and possibly diltiazem reduces mortality and morbidity, except in patients with congestive heart failure without signs of reversible myocardial ischaemia. Nifedipine may have negative effects. The efficacy of the second-generation dihydropyridines remains to be demonstrated.

Angiotensin-Converting Enzyme Inhibitors↗