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Biomedical subjects

T L Sørensen

Publications and source records attributed to T L Sørensen.

At least 19 recordsLinked to original sources
PubMed2005

CD26 + CD4 + T cell counts and attack risk in interferon-treated multiple sclerosis.

Biomarkers that allow the identification of patients with multiple sclerosis (MS) with an insufficient response to immunomodulatory treatment would be desirable, as currently available treatments are only incompletely efficacious. Previous studies have shown that the expression of CD25, CD26 and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-beta-treated patients, we found that the hazard ratio for developing an attack was 28 in patients with CD26 + CD4 + T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-beta antibodies. CD26 + CD4 + T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-beta.

Adjuvants, Immunologic↗
PubMed2004

Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis.

The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS.

Adult↗
PubMed2004

Optic neuritis: chemokine receptor CXCR3 and its ligands.

AIM: To study the involvement of the chemokine receptor CXCR3 and its ligands (CXCL9/Mig, CXCL10/IP-10, CXCL11/ITAC) in optic neuritis (ON). METHODS: 30 patients with ON and 10 non-inflammatory neurological disease controls were included. The patients underwent a phlebotomy, lumbar puncture, and MRI scan. CXCR3 expression was studied on blood and cerebrospinal fluid (CSF) T cells by flow cytometry. CXCL9, CXCL10, and CXCL11 were measured in plasma and CSF by ELISA. RESULTS: CSF concentrations of CXCL10, but not of CXCL9 and CXCL11, were significantly higher in ON patients than in controls. CSF concentrations of CXCL10 correlated with the CSF leucocyte count in ON patients, and CXCR3 expressing cells were significantly enriched in the CSF. CONCLUSION: These data show that the CSF concentration of the CXCR3 ligand CXCL10 is selectively increased in CSF from ON patients, and CXCR3 positive cells are recruited to the subarachnoid space.

Adult↗
PubMed2003

Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system.

Chemokines and matrix metalloproteinases (MMPs) play key roles in leukocyte migration across the blood-brain barrier (BBB) in infectious and inflammatory diseases, including multiple sclerosis (MS). In MS some chemokine receptors are expressed by an increased percentage of T cells in blood, the CSF concentration of chemokine ligands for these receptors is increased, and there is accumulation of T cells expressing relevant chemokine receptors in CSF and in the CNS parenchyma. Chemokine receptor expression patterns appear to reflect disease activity and disease stage in MS. MMPs are constitutively expressed or induced by proinflammatory cytokines and chemokines in leukocytes and CNS-resident cells. Several MMPs are expressed in MS plaques, and the CSF concentration of MMP-9 is increased in MS. The CSF concentration of MMP-9 may reflect disease activity in MS, and the CSF concentration of MMP-9 is higher in patients carrying the MS-associated HLA type DRB1 1501. We review how chemokines and MMP-9 may be involved in the pathogenesis of MS by controlling leukocyte migration between different functional compartments. Measuring expression of these molecules may find use as surrogate markers of disease activity in MS, and interfering with their function holds promise as a novel therapeutic strategy in MS.

Animals↗
PubMed2003

Evidence favoring the involvement of CC chemokine receptor (CCR) 5 in T-lymphocyte accumulation in optic neuritis.

OBJECTIVE: To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON). MATERIALS AND METHODS: Expression of CCR5 and related receptors CCR1 and CCR3 on CD4- and CD8-positive T-cells in peripheral blood mononuclear cells (PBMC) and CSF was determined by flow cytometry in 20 patients with ON, 16 control patients with lumbar spondylosis, 20 healthy controls (HC) and 16 patients with rheumatoid arthritis (RA). RESULTS: CCR5+CD4+ and CD8+ T-cells were enriched in CSF, compared with PBMC, in both ON and CON patients (all P < 0.001), and the percentages of CD4+/CCR5+ (r = 0.917) and CD8+/CCR5+ (r = 0.828) cells in PBMC and CSF were strongly and directly correlated. CCR5+ T-cells produce high amounts of tumor necrosis factor-alpha (TNF-alpha) and very low amounts of interleukin-5 (IL-5). Closely related receptors (CCR1, CCR3) were not altered. CONCLUSIONS: Our data suggest an involvement of CCR5 in T-cell accumulation in the inflamed central nervous system.

Adult↗
PubMed2003

Prevalence of resistance to ampicillin, gentamicin and vancomycin in Enterococcus faecalis and Enterococcus faecium isolates from clinical specimens and use of antimicrobials in five Nordic hospitals.

We determined the species distribution and prevalence of ampicillin resistance, high-level gentamicin resistance (HLGR) and vancomycin resistance among clinical enterococcal isolates from five Nordic laboratories (Bergen, Tromsø, Uppsala, Aarhus and Reykjavik). Isolates represented three different groups: (i) all blood culture isolates from 1999; (ii) consecutive in-patient isolates (maximum 40); and (iii) consecutive outpatient isolates (maximum 40) collected during March to May 2000. Antimicrobial use data were collected at the national and hospital level. A high proportion (31.4%) of Enterococcus faecium was detected among blood culture isolates, in contrast to only 4.2% among isolates from outpatients. Ampicillin resistance was not found in Enterococcus faecalis, in contrast to 48.8% in E. faecium isolates. HLGR rates varied considerably between laboratories (1.1-27.6%). Acquired vancomycin resistance was not detected. There were no significant differences in the prevalences of HLGR between in-patient and outpatient isolates at individual hospitals. A cluster of clonally related ampicillin-resistant and HLGR E. faecium isolates was demonstrated in one of the hospitals. The lowest level of hospital antimicrobial use, the lowest proportion of E. faecium and the lowest prevalence of resistance were observed in Reykjavik. The study showed a relatively low level of resistance in enterococci, as compared with most European countries and the USA. However, there were large differences between hospitals with regard to the relative proportion of E. faecium isolates, their susceptibility to ampicillin and gentamicin, as well as the prevalence of HLGR in E. faecalis isolates. This indicates a potential for further improvement of antibiotic policies, and possibly hospital infection control, to maintain the low resistance levels observed in these countries.

Ampicillin Resistance↗
PubMed2003

Respiratory syncytial virus infection--risk factors for hospital admission: a case-control study.

UNLABELLED: Most infants are infected with respiratory syncytial virus (RSV) during the first 2 y of life. The majority have only a mild upper respiratory tract infection, but 1-2% develop a more severe illness and are admitted to hospital. AIM: To carry out a study of risk factors for hospital admission because of RSV infection in Denmark in children aged less than 2 y of age. METHODS: The study population included all 1252 children admitted to hospital with verified RSV infection in two Danish counties during the 5-y period 1990-1994. The investigation comprised a retrospective case-control study with five matched controls per case. In a multivariate analysis the risk factors included medical and demographic variables, and in infants <3 mo of age at hospitalization, two aspects of innate immunity: mannose-binding lectin (MBL) concentration and maternal RSV serum antibody titre, measured on eluates from stored dried blood from the infants' 4th day of life. The effect of each risk factor is expressed as an odds ratio, corresponding to the relative risk of being a case rather than a control if the risk factor is present. RESULTS: The following independent risk factors were identified: age, sex, month of birth, gestational age, birthweight, presence of a sibling, up to 5 y older than the case, and maternal smoking during pregnancy. There was a marginal effect of maternal RSV antibody levels, but no effect of neonatal serum MBL concentration or of crowding in the household. CONCLUSIONS: Ninety percent of cases and 80% of controls had one or more risk factors. Even though several factors were found to increase the risk for hospitalization for RSV disease, all the effects were small and no single specific factor could be identified to explain the hospitalization of the minority of children with RSV infection.

Age Factors↗
PubMed2002

T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking.

It is believed that chemokines and their receptors are involved in trafficking of T-cells to the central nervous system (CNS). The aim of the current study was to define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine receptors associated with trafficking to sites of inflammation. Flow cytometry was used to detect chemokine receptor expression. We observed that CD3+T-cells in the CSF express a restricted array of inflammatory chemokine receptors, specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was independent of the presence of CNS inflammation, since comparable findings were obtained in patients with multiple sclerosis (MS) and individuals with non-inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T-cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells in the inflamed CNS.

Adult↗
PubMed2002

Selective suppression of chemokine receptor CXCR3 expression by interferon-beta1a in multiple sclerosis.

We studied the expression of chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR3 on CD4 and CD8 positive T cells, and on CD14 positive monocytes in blood from 10 patients with relapsing-remitting multiple sclerosis (MS) at initiation of interferon (IFN)-beta treatment, after 1 month and after 3 months of treatment. It was found that the expression of CXCR3 on CD4+ and CD8+ T cells was significantly reduced after 3 months of treatment. The expression of other receptors was unaltered. Since CXCR3 cells are enriched in cerebrospinal fluid (CSF), and are detected in lesion material in MS this may represent an important mode of action of interferon-beta in MS.

Adult↗
PubMed2001

Distinct chemokine receptor and cytokine expression profile in secondary progressive MS.

BACKGROUND: Chemokines, small chemotactic cytokines, have been implicated in active relapsing-remitting MS (RRMS). However, the role of chemokines and chemokine receptors has not been specifically studied in secondary progressive MS (SPMS). METHODS: Fifteen patients with SPMS, 15 patients with relapses of RRMS, 10 patients with RRMS in remission, and 20 healthy controls were included in this study. The expression of CC chemokine receptor 1(CCR1), CCR2, CCR3, CCR5, and CXC chemokine receptor 3(CXCR3) was studied on leukocyte subsets using flow cytometry, and the cytokine profile of T cells expressing CCR2 and CCR5 was determined. The authors also studied the effect of treatment with interferon-beta-1b on the expression of chemokine receptors in SPMS. RESULTS: The authors found a significantly higher percentage of CCR2-expressing T cells in SPMS than in the other patients groups. CCR2-positive T cells produced high levels of interleukin (IL)-5 and low levels of tumor necrosis factor alpha, indicating a T-helper type 2 (Th2)/T-cytotoxic type 2 (Tc2) profile of these cells. The expression of CCR5, a chemokine receptor associated with Th1 responses, was significantly lower in SPMS than in patients with active RRMS. Interferon (IFN) beta-1b treatment in SPMS did not alter chemokine receptor expression in SPMS. CONCLUSION: The authors find qualitative differences in the systemic inflammatory response in RRMS and SPMS, indicating a distinct inflammatory environment in SPMS. Chemokine receptor expression in SPMS did not change after treatment with IFN beta-1b. It remains to be established if these findings reflect differences between RRMS and SPMS in effector or regulatory mechanisms.

Adjuvants, Immunologic↗
PubMed2001

Transient intestinal carriage after ingestion of antibiotic-resistant Enterococcus faecium from chicken and pork.

BACKGROUND: Antibiotic-resistant enterococci are often present in retail meats, but it is unclear whether the ingestion of these contaminants leads to sustained intestinal carriage. METHODS: We conducted a randomized, double-blind study in 18 healthy volunteers. Six ingested a mixture of 10(7) colony-forming units (CFU) of two glycopeptide-resistant strains of Enterococcus faecium obtained from chicken purchased at a grocery store, six ingested 10(7) CFU of a streptogramin-resistant strain of E. faecium obtained from a pig at slaughter, and six ingested 10(7) CFU of a glycopeptide-susceptible and streptogramin-susceptible strain of E. faecium from chicken purchased at a grocery store. Suspensions of enterococci were prepared in 250 ml of whole milk and were well within the amounts deemed acceptable by Danish food regulations. Stool samples were collected before exposure, daily for 1 week after ingestion, and at 14 and 35 days. Resistant enterococci in stools were identified by selective culture techniques; further molecular characterization of the organisms was also conducted. RESULTS: At the outset, none of the subjects were colonized with glycopeptide-resistant or streptogramin-resistant E. faecium. After ingestion of the study strains, these same strains were isolated from the stools of all subjects, in various concentrations. The test strain was isolated in stool from 8 of 12 subjects on day 6, and from 1 of 12 on day 14. All stool samples were negative at 35 days. CONCLUSIONS: The ingestion of resistant E. faecium of animal origin leads to detectable concentrations of the resistant strain in stools for up to 14 days after ingestion. The organisms survive gastric passage and multiply.

Adult↗
PubMed2001

CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis.

Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5 and macrophage inflammatory protein-1alpha/CCL3. We analyzed expression of CCR1 and CCR5, the monocyte receptors for these chemokines, on circulating and cerebrospinal fluid CD14+ cells, and in MS brain lesions. Approximately 70% of cerebrospinal fluid monocytes were CCR1+/CCR5+, regardless of the presence of CNS pathology, compared to less than 20% of circulating monocytes. In active MS lesions CCR1+/CCR5+ monocytes were found in perivascular cell cuffs and at the demyelinating edges of evolving lesions. Mononuclear phagocytes in early demyelinating stages comprised CCR1+/CCR5+ hematogenous monocytes and CCR1-/CCR5- resident microglial cells. In later stages, phagocytic macrophages were uniformly CCR1-/CCR5+. Cultured in vitro, adherent monocytes/macrophages up-regulated CCR5 and down-regulated CCR1 expression, compared to freshly-isolated monocytes. Taken together, these findings suggest that monocytes competent to enter the CNS compartment derive from a minority CCR1+/CCR5+ population in the circulating pool. In the presence of ligand, these cells will be retained in the CNS. During further activation in lesions, infiltrating monocytes down-regulate CCR1 but not CCR5, whereas microglia up-regulate CCR5.

Adult↗
PubMed2001

Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis.

Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation.

Anti-Inflammatory Agents↗
PubMed2001

The patient, their doctor, the regulator and the profit maker: conflicts and possible solutions.

The dilemmas and conflicts between industry, who develop and market antibiotics and the regulators who are responsible for regulating their use to preserve efficacy are explored. Despite regulations, the industry remains profitable and should concentrate more on development of innovative products which readily gain market share without excessive marketing. Various aspects of regulations are discussed as they influence the prescriber and the patient.

Anti-Bacterial Agents↗
PubMed2000

Control of antibiotic use in the community: the Danish experience.

The selection pressure for antibacterial resistance in the community might not be as high as in hospitals. However, it is generally accepted that it is in the primary healthcare sector that one can achieve the greatest decrease in the total use of antimicrobials. There are significant differences in the overall use of antimicrobials among European countries. On average, 80% to 90% of the total antibiotic use in each country takes place in the primary healthcare sector. Surveillance of the use of antimicrobials is the core for planning interventions and monitoring their effect. These interventions may be implemented for either political, economic, or professional reasons. Often, but not always, political interventions are governmental, and professional interventions are recommendations from professional associations. Examples of interventions at different levels in the Danish healthcare system, from the general practitioner to legislation by the government, will be presented together with their effect on the use of antimicrobials.

Anti-Bacterial Agents↗
PubMed1999

Optic neuritis as onset manifestation of multiple sclerosis: a nationwide, long-term survey.

OBJECTIVE: To determine the predictive value on survival of optic neuritis (ON) as onset manifestation of MS. METHODS: We used data obtained from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark. From 1949 to 1990, 7,548 unselected patients fulfilling standardized diagnostic criteria of MS were registered. RESULTS: The onset manifestation of MS was known in 6,923 patients, and was ON in 1,282 patients (19%). The mean age at onset was 31.1 years for these patients compared with 34.8 years for patients with another or unknown onset manifestation of MS (non-ON) (p < 0.001). The mean delay from the first known manifestation of MS to the final diagnosis of MS was 6.1 years (ON) and 4.2 years (non-ON). The median survival time from onset of ON was 30 years in men (compared with 41 years in the matched general male population) and 40 years in women (versus 47 years). The excess death rate increased with age at onset of MS in people of each sex. Excess death rate for women differed significantly between patients with ON as onset manifestation and patients with another or unknown onset manifestation of MS (8.3 versus 13.0). In patients with ON as onset manifestation of MS, the excess death rate was significantly higher in men (14.0) than in women (8.3). CONCLUSION: ON as onset manifestation of MS indicates a more favorable prognosis of survival of MS judged by excess death rate only in women.

Adolescent↗