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Biomedical subjects

S Larsson

Publications and source records attributed to S Larsson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M(1 )and M(2) muscarinic acetylcholine receptors in Alzheimer's disease.

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-IQNP) has high affinity to the M(1 )and M(2) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.

Alzheimer Disease↗
PubMed1999

Open MR imaging of the unstable shoulder in the apprehension test position: description and evaluation of an alternative MR examination position.

The aim of this study was to describe and evaluate an alternative MR assessment procedure for analysis of unstable shoulders. Twelve patients with unilateral recurrent anterior shoulder dislocation had both shoulders examined. Magnetic resonance imaging was performed with an open-MR system in the apprehension position with the shoulder in 90 degrees of abduction and maximum tolerable external rotation. Contrast enhancement was achieved with intravenous gadolinium. Correlations were made to the findings at operation. In 10 of 12 unstable shoulders the inferior glenohumeral ligament labral complex (IGHLLC) was detached from the glenoid as seen on MR and later verified during surgery. In one shoulder MR was unable to show a capsulolabral detachment that was verified at surgery, whereas in one shoulder both MR and surgical assessment revealed no soft tissue detachment (accuracy 92 %). A Hill-Sachs lesion was visualized and verified in all unstable shoulders, whereas the stable controls revealed normal IGHLLC and no Hill-Sachs lesion. Open-MRI evaluation of the shoulder in the apprehension test position may become a useful tool for the evaluation of anterior shoulder instability.

Adult↗
PubMed1999

Influence of aortic valve replacement, prosthesis type, and size on functional outcome and ventricular mass in patients with aortic stenosis.

OBJECTIVES: Two years after surgery for severe aortic stenosis, we prospectively evaluated the influence of aortic valve replacement, as well as valve type (mechanical or stented biologic) and size, on functional status, left ventricular function, and regression of mass. METHODS: Patients who received either a mechanical (n = 95) or a biologic valve (n = 42) were studied by echocardiography before the operation and after 2 years. RESULTS: The percentage of patients with severe dyspnea decreased from 53% to 13% (P =.001). The cardiac index increased from mean 2.6 L/min per square meter (95% CI: 2.48-2. 72 L/min per square meter) to 3.1 L/min per square meter (95% CI: 2. 94-3.26 L/min per square meter; P =.001). The percentage of the patients with mild-to-moderate diastolic dysfunction decreased from 43% to 18% (P =.001). The left ventricular mass index was reduced by 42.4 g (95% CI: 35-50 g; P =.001). In comparison with biologic valves of the same size, mechanical valves produced a more pronounced reduction in mass index (overall difference 21.7 g; 95% CI: 37.1-6.4 g; P =.007) and a lower mean Doppler gradient (overall difference 4 mm Hg; 95% CI: 2-6 mm Hg; P =.0002). CONCLUSIONS: Patients undergoing aortic valve replacement had an improvement in functional status, as well as systolic and diastolic left ventricular function, and a reduction in left ventricular mass index, irrespective of prosthesis size and type. Mechanical valves are somewhat less obstructive than stented bioprosthetic valves of the same size. They are also associated with a concomitantly more pronounced reduction of left ventricular mass.

Aged↗
PubMed1999

Cutaneous delayed-type hypersensitivity reactions in smokers with chronic bronchitis and recurrent exacerbations: comparison with asymptomatic smokers and never-smokers.

The aim of the present study was to investigate whether smoking patients with chronic bronchitis (CB) and recurrent exacerbations show signs of depressed cell-mediated immunity (CMI), as reflected in the cutaneous delayed-type hypersensitivity (DTH) reaction, in comparison with asymptomatic smokers and healthy never-smokers. The study was a comparative clinical study performed at a university hospital center of respiratory medicine. Sixteen smokers with stable CB and recurrent exacerbations, five of whom had mild airflow obstruction, 18 asymptomatic smokers and 18 healthy never-smokers, all aged between 35 and 64 years, participated. No subjects treated with corticosteroids or N-acetylcysteine were included. Cutaneous DTH-reactions to seven recall antigens were assessed with Multitest, a standardized in vivo test of clinical CMI. Reactions were assessed 48 h after application by measurement of skin induration. A score (sum in mm of positive reactions) was created to assess overall reactivity. Neither the score nor the number of positive reactions differed significantly between the three study groups. Men had a significantly higher reactivity than women (P < 0.05) irrespective of group affiliation. No influence of smoking status on DTH reactivity could be seen. In the CB group no correlation was found between DTH reactivity and number of exacerbations the past 2 years. Patients with chronic bronchitis and recurrent exacerbations did not differ from asymptomatic smokers or healthy never-smokers with respect to cutaneous DTH reactions. Depression of CMI, as measured in this study, does not seem to be a primary factor behind recurrent exacerbations in smokers with CB.

Bronchitis↗
PubMed1999

In vivo dynamic distribution of 131I-glucagon-like peptide-1 (7-36) amide in the rat studied by gamma camera.

The in vivo distribution of glucagon-like peptide-1 (7-36) amide (GLP-1) was studied in a rat model using radiolabeled GLP-1 (131I-GLP-1) depicted by a gamma-camera. The dynamic scan showed a rapid clearance from the blood circulation after an intravenous (i.v.) injection of 131I-GLP-1. After 10 min, the major part of the radioactivity was accumulated in the kidneys, whereas about 9% (of the blood value) was found in the brain. The pharmacokinetic study using 125I-GLP-1 demonstrated a rapid elimination from plasma, with a half-life of 3.3 +/- 0.6 min, a clearance of 117 +/- 15 mL/min, and a distribution volume of 557 +/- 61 mL. The elimination half-lives for the intact 125I-GLP-1 in lungs and kidneys were determined to 3.7 and 3.9 min, respectively. The metabolite GLP-1 (9-36) amide was followed in blood, lung, and kidney. All other organs assumed to contain low molecular weight fragments of GLP-1. The present study suggest that GLP-1 and/or its labeled metabolites cross the blood-brain barrier. Also the kidney plays an essential role in GLP-1 elimination after an i.v. administration, which can be of clinical interest especially in patients with kidney insufficiency who are treated with GLP-1.

Animals↗
PubMed1999

Biodistribution of liposomal 131I-VIP in rat using gamma camera.

Vasoactive intestinal peptide (VIP), a 28 amino-acid peptide was labeled with 131I and encapsulated into liposomes. 131I-VIP or liposomal 131I-VIP was administered intravenously into the rats. The distribution was studied by a gamma camera and established by counting the radioactivity in the removed organs. The elimination half-life for the liposomal 131I-VIP in both blood and lungs was significantly longer (5.29 and 9.28 min, respectively) than that obtained after the administration of 131I-VIP (0.62 and 3.18 min, respectively). Dynamic scans using a gamma camera after the administration of liposomal 131I-VIP showed a higher uptake of the liposomal form into the lungs compared with 131I-VIP. The lack of VIP in asthmatics has been shown in previous studies. However, the clinical investigations using VIP were disappointing most probably due to the rapid degradation of the peptide in the bronchial tract. This in fact is supported by our previous study, in which we demonstrated that VIP had a half-life of 0.45 min in blood. We conclude that the encapsulation of VIP in liposomes prolongs its elimination half-life in plasma and enhances its uptake in lungs. This observation may increase the clinical use of VIP in both diagnostic and therapy.

Animals↗
PubMed1999

Gender differences in patients with severe aortic stenosis: impact on preoperative left ventricular geometry and function, as well as early postoperative morbidity and mortality.

OBJECTIVE: In patients with severe aortic stenosis, we studied the impact of gender on preoperative left ventricular geometry and function, as well as on early postoperative mortality and morbidity. METHODS: Prospective Doppler echocardiographic evaluation was performed in 99 female patients and 96 males. RESULTS: The patients had severe aortic stenosis and the mean pressure gradients were similar in females and males. Left ventricular diastolic volume adjusted for body surface area (BSA) was larger in males, 55+/-17.4 ml/m2 versus 43+/-13.1 mL/m2 (mean+/-standard deviation; P = 0.0001). The ejection fraction was similar in females (55+/-14%) and males (55+/-13%), and patients of both sexes had significantly lower stroke volume and cardiac index than healthy controls. The relative wall thickness (wall thickness/diastolic diameter ratio) was higher (P = 0.03) in females (0.47+/-0.10) than in males (0.43+/-0.10) Consequently, the diastolic diameter/wall thickness ratio (a substitute for wall tension) was higher (P = 0.02) in males (4.2+/-0.99) than in females (3.9+/-0.80). Compared with survivors, patients who died within 30 days of the operation (n = 17, 11 females) had a smaller body surface area (1.70+/-0.19 vs. 1.82+/-0.19 m2, P = 0.012), smaller left ventricular outflow tract (20.8+/-0.21 vs. 22.0+/-0.22 mm, P = 0.023), higher incidence of abnormal intraventricular flow velocity (33 vs. 8%, P = 0.018) and increased relative wall thickness (0.52+/-0.17 vs. 0.45+/-0.09 P = 0.039). Gender was of no independent importance for early mortality when age and left ventricular outflow tract diameter were accounted for. CONCLUSIONS: Cardiac adaptation to aortic stenosis seems to be influenced by gender, males presenting larger left ventricular volumes and higher wall tension. The echocardiographic findings of a narrow left ventricular outflow tract, abnormally increased intraventricular velocity and increased relative wall thickness identified patients with increased risk of early postoperative mortality. However gender had no independent impact on early postoperative outcome.

Aortic Valve↗
PubMed1999

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.

Administration, Oral↗
PubMed1999

IL-2 and IL-4 counteract budesonide inhibition of GM-CSF and IL-10, but not of IL-8, IL-12 or TNF-alpha production by human mononuclear blood cells.

1. The combination of interleukin-2 (IL-2) and IL-4 reduces the inhibitory effects of glucocorticoids on granulocyte-macrophage colony-stimulating factor (GM-CSF) production, in agreement with the hypothesis that this combination causes glucocorticoid resistance. Whether a general cytokine resistance to glucocorticoids is induced by IL-2 and IL-4 has not been reported. 2. Mononuclear blood cells from healthy individuals were pre-treated with IL-2, IL-4, or IL-2+ IL-4 (31.3-500 U ml(-1)) for 48 h, prior to lipopolysaccharide (LPS; 10 ng ml(-1); 20 h) and budesonide addition. Cytokine levels in the supernatants were analysed using specific immunoassays. DNA content was analysed to estimate cell numbers. 3. GM-CSF production was totally inhibited by budesonide at 10(-8) M in vehicle treated cultures, while IL-10 was inhibited to 33.4+/-4.3% of control. IL-2, IL-4, or IL-2 + IL-4 reduced the inhibitory effects of budesonide on GM-CSF to similar levels (23.7 6.7, 31.6+/-8.5 and 35.1+/-4.3% of control, respectively). IL-2, IL-4, or IL-2 + IL-4 also reduced the inhibitory effects of budesonide on IL-10 production (46.5+/-6.6, 55.9+/-7.3%, and 68.3+/-9.9% of control, respectively). In contrast, IL-8, IL-12 and TNF-alpha production did not become resistant to budesonide. 4. Thus, glucocorticoid resistance induced by IL-2 and IL-4 is not general at the cytokine production level. While the glucocorticoid sensitivity of GM-CSF and IL-10 production decreased, the sensitivity of IL-8, IL-12 or TNF-alpha production was unchanged. Also, the mixture of IL-2 and IL-4 is not crucial for induction of glucocorticoid resistance of GM-CSF production.

Budesonide↗
PubMed1999

Long-term effects of a pulmonary rehabilitation programme in outpatients with chronic obstructive pulmonary disease: a randomized controlled study.

Fifty patients with severe chronic obstructive pulmonary disease (FEV1 < 50% pred.) were randomized to a rehabilitation group and a control group. The rehabilitation group took part in an individualized multidisciplinary, outpatient 12-month rehabilitation programme. Exercise training was intensive during the first 6 weeks and was then gradually replaced by an individual home-training programme and booster sessions. Controls received the usual outpatient care. Positive effects were found in terms of maximum symptom-limited exercise tolerance and walking distance (13.5 and 12.1% increase, respectively) in the rehabilitation group compared with the controls. Quality of life measurements showed minor beneficial effects on the Sickness Impact Profile, indicating a higher level of activity. No effect was seen on the St George's Respiratory Questionnaire or the Mood Adjective Check List. Patients expressed their enthusiasm for the rehabilitation programme in a study-specific questionnaire.

Aged↗
PubMed1999

No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures.

OBJECTIVE: To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod. DESIGN: Prospective, randomized, double blinded, and placebo controlled. PATIENTS AND METHODS: Thirty-two adult patients were included, fifteen in the active ultrasound group and seventeen in the placebo group. They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive. Standardized radiographs were taken every third week until healing and at six and twelve months. All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon. The codes were not broken until all fractures had healed and all radiographs had been evaluated. RESULTS: The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo (p=0.44). The healing time, defined as radiologic bridging of three cortices, was on average 155+/-22 days (median 113 days) for the active treatment group and 125+/-11 days (median 112 days) for the placebo group (p=0.76) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group (p=0.40) as evaluated by the orthopaedic surgeon. CONCLUSION: We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail. Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound.

Adolescent↗
PubMed1999

Increased levels of interleukin-16 in the airways of tobacco smokers: relationship with peripheral blood T lymphocytes.

BACKGROUND: The mechanisms behind the development of systemic immunomodulation among tobacco smokers are not fully understood, but several studies have indicated a role for CD8+ and/or CD4+ T cells. Interleukin (IL)-16, a cytokine released from inflammatory cells as well as bronchial epithelial cells, can recruit and activate CD4+ T cells. A study was undertaken to establish whether the IL-16 level is increased in the airways of tobacco smokers and to determine whether airway levels of IL-16 are related to the number and function of systemic T lymphocytes. METHODS: Bronchoalveolar lavage (BAL) fluid was collected from eight never smokers and 18 tobacco smokers without clinical airway symptoms, and from 16 tobacco smokers with clinical airway symptoms. Interleukin-16 protein levels in BAL fluid were determined using enzyme-linked immunosorbent assay (ELISA). Peripheral blood was collected for determination of CD4+ T cell content using flow cytometry. The responsiveness of systemic lymphocytes in smokers was assessed by measuring the proliferative response of peripheral blood lymphocytes to the superantigen staphylococcus enterotoxin A (SEA). RESULTS: The IL-16 protein level in the BAL fluid was significantly higher in tobacco smokers than in non-smokers. However, among tobacco smokers the IL-16 level was similar in asymptomatic smokers and in those with airway symptoms. The level of IL-16 in the BAL fluid of smokers correlated negatively with the percentage of CD4+ T cells and positively with superantigen stimulated lymphocyte proliferation in peripheral blood. CONCLUSIONS: In tobacco smokers the airway IL-16 level is increased and it is possible that this increase in IL-16 influences systemic immunomodulation by altering the number and responsiveness of systemic T lymphocytes.

Adult↗
PubMed1999

Characterisation of genetic diversity in potential biomass willows (Salix spp.) by RAPD and AFLP analyses.

The genus Salix (willow) contains a number of species which have great potential value as biomass crops in short rotation coppice (SRC). Efforts to improve biomass willows by breeding are currently hampered by the limited information available on genetic diversity and on genetic relationships within and among species, clones, and hybrids in the gene pool. Hybridisation occurs commonly in nature and the relatedness of many clones is unclear. Molecular markers were used to assess genetic diversity in a reference set of willows maintained within the U.K. National Collection and 16 elite clones currently being evaluated in field trials at several European sites. The two marker systems tested, RAPDs and AFLPs, were equally informative for revealing relationships within the reference set of clones. No differences were observed when alternative similarity coefficients were compared or when analysis was restricted to the use of polymorphic bands only. Good agreement with available knowledge of the clonal origins was obtained and one instance of duplicate clones was identified. AFLPs revealed more genetic diversity and discriminated between closely related clones. A difference in the relationships revealed was observed with one AFLP primer combination. RAPDs were more problematic, both in terms of reproducibility and scorability.

DNA, Plant↗
PubMed1999

Serum bone markers after intramedullary fixed tibial fractures.

Serum levels of bone markers were measured prospectively for 1 year in 30 adult patients with an intramedullary fixed tibial fracture. In a double blinded design, half of the patients received low intensity ultrasound. All fractures healed, although in seven of 30 the healing was delayed more than 6 months. There was no significant difference in radiologic healing time between the ultrasound group (median, 113 days) and the placebo group (median, 112 days). The marker for bone resorption, crosslinked telopeptide, peaked at 1 to 4 weeks, whereas markers for bone formation peaked at 10 to 16 weeks for bone specific alkaline phosphatase and osteocalcin. Crosslinked telopeptide was lower at 1 week in patients treated with ultrasound than in those receiving placebo. Patients with delayed healing did not differ in crosslinked telopeptide compared with patients with normal healing. There were no differences in bone formation markers between patients who received ultrasound or placebo. Patients with delayed healing had lower levels of bone specific alkaline phosphatase between 4 and 7 weeks than did patients with normal healing, although no such differences were seen for osteocalcin. The results indicate that low intensity ultrasound might slow bone resorption, although there is no visible effect on bone formation. Patients with delayed healing had adequate bone resorption but slower early bone formation than did patients with normal healing.

Adult↗
PubMed1998

Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to have antianginal and anti-ischemic effects in severe angina pectoris. The present study was performed to investigate whether SCS can be used as an alternative to coronary artery bypass grafting (CABG) in selected patient groups, ie, patients with no proven prognostic benefit from CABG and with an increased surgical risk. METHODS AND RESULTS: One hundred four patients were randomized (SCS, 53; CABG, 51). The patients were assessed with respect to symptoms, exercise capacity, ischemic ECG changes during exercise, rate-pressure product, mortality, and cardiovascular morbidity before and 6 months after the operation. Both groups had adequate symptom relief (P<.0001), and there was no difference between SCS and CABG. The CABG group had an increase in exercise capacity (P=.02), less ST-segment depression on maximum (P=.005) and comparable (P=.0009) workloads, and an increase in the rate-pressure product both at maximum (P=.0003) and comparable (P=.03) workloads compared with the SCS group. Eight deaths occurred during the follow-up period, 7 in the CABG group and 1 in the SCS group. On an intention-to-treat basis, the mortality rate was lower in the SCS group (P=.02). Cerebrovascular morbidity was also lower in the SCS group (P=.03). CONCLUSIONS: CABG and SCS appear to be equivalent methods in terms of symptom relief in this group of patients. Effects on ischemia, morbidity, and mortality should be considered in the choice of treatment method. Taking all factors into account, it seems reasonable to conclude that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications.

Adult↗
PubMed1998

Productive cytomegalovirus (CMV) infection exclusively in CD13-positive peripheral blood mononuclear cells from CMV-infected individuals: implications for prevention of CMV transmission.

BACKGROUND: Monocytes are suggested to harbor latent cytomegalovirus (CMV) in peripheral blood, which concurs with the finding that all CMV-susceptible cells carry the CD13 surface molecule. Here, we investigated whether all latently and productively CMV-infected peripheral blood mononuclear cells (PBMCs) could be eliminated by depletion of CD13-expressing cells. METHODS: Depletion of CD13-positive cells was performed with monoclonal antibodies and magnetic cell separation (MACS) beads followed by MACS. CMV DNA and cDNA were amplified by polymerase chain reaction with specific primers for two CMV genes, major immediate early and phosphoprotein 150. The presence of infectious virus was tested by incubating homogenized in vitro- or in vivo-infected PBMCs with human fibroblasts. CMV infection of fibroblasts was detected by intracellular expression of CMV proteins. RESULTS: Elimination of CD13-positive PBMCs removed productively in vitro- and in vivo-infected cells, as demonstrated by detection of infectious virus only in PBMC fractions containing CD13-positive cells. In support of this finding, CMV RNA was not detected in pure CD13-negative cell fractions. Furthermore, CMV DNA was found exclusively in CD13-positive PBMCs obtained from patients with acute CMV infection. CONCLUSIONS: Our data suggest that CMV replicates exclusively in CD13-positive PBMCs. These findings have important clinical applications, because the elimination of CD13-positive cells may reduce the risk for transmission of latent CMV in blood products and bone marrow grafts and thereby also decrease the risk for CMV-induced complications, such as chronic graft-versus-host disease in bone marrow transplant patients.

Adult↗