Biomedical subjects

A L Laursen

Publications and source records attributed to A L Laursen.

17 recordsLinked to original sources

PubMed2001

The impact of CMV on the respiratory burst of macrophages in response to Pneumocystis carinii.

Infection of human monocyte-derived macrophages with CMV decreased the respiratory burst when cells were stimulated with opsonized zymosan or Pneumocystis carinii (P. carinii). Such an effect, though smaller, was also seen with heat-inactivated CMV, but only when triggered by zymosan. The effect was most pronounced in cells obtained from CMV antibody-negative donors. Dexamethasone further reduced the respiratory burst, both in uninfected and CMV-infected cells. Interferon-gamma increased the response in uninfected cells and, to a lesser extend, in cells treated with heat-inactivated CMV, whereas no effect was seen with infective CMV. No overt productive infection or cytopathology could be detected, however, the monocytes incubated with infective but also heat-inactivated CMV formed clusters, a phenomenon that was equally pronounced in cultures from CMV antibody positive and negative-donors. These results might help explain the worse prognosis of P. carinii pneumonia in patients coinfected with CMV and receiving dexamethasone.

Animals↗

PubMed2000

[Zoonoses among immigrants].

During the last ten years Denmark has received an increasing number of immigrants, especially from the Balkans, the Middle East, and Somalia. Some of these may suffer from the zoonoses occurring in their country of origin. But apart from echinococcosis, zoonoses in these immigrants do not seem to pose a quantitatively greater problem than in Danes who have visited these areas. However it is important to have a knowledge of the symptoms and mode of transmission of zoonoses occurring in areas where the immigrants come from.

Brucellosis↗

PubMed1998

Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C: results of a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment.

Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU TIW. At 6 months, 25 patients with a complete or a partial biochemical response were randomly allocated to either a fixed dose regimen (13 patients) (3 or 6 MU thrice weekly) or an individualized dose regimen (12 patients) tapering interferon dose from 3 or 6 MU by one-third every 2 months if transaminases were persistently normal. The remaining 22 biochemical nonresponders were followed for an additional 6 months without further treatment. After 12 months of treatment, 18 patients (38%) had a virological response, irrespective of regimen, and seven patients (16%) had a sustained virological and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable to that obtained in previous studies among nonhaemophiliacs. However, a sustained virological and biochemical response was seen in only 16% of treatment patients.

Adolescent↗

PubMed1998

Low levels of IgG antibodies against pneumocystis carinii among HIV-infected patients.

IgG antibodies against Pneumocystis carinii (P. carinii) were detected by an ELISA method using urea-extracted material from human and rat P. carinii as the antigen. Carbohydrate formed a major part of the antigen responsible for reactivity in the ELISA assay, since periodate treatment reduced the reactivity of most sera tested. Cross-reactivity between human and rat P. carinii was detected. However, human serum recognized antigens specific for human P. carinii. With the ELISA method IgG antibody levels were compared between blood donors (n = 40), asymptomatic HIV-antibody positive patients (n = 30) and AIDS patients with (n=22) and without previous P. carinii pneumonia (PCP) (n=21). HIV-infected patients had significantly lower antibody reactivity against the microorganism compared with blood donors. Among HIV-antibody positive patients the highest antibody reactivity was seen in PCP patients. The antibody response to PCP was impaired, since an equal number of patients had an increase and a decrease in antibody reactivity. In conclusion, carbohydrate formed an important part of the P. carinii immunogenic antigen. Cross-reactivity between rat and human P. carinii was demonstrated, but reactivity was somewhat lower using antigen from rats. The antibody level was lower in HIV-infected patients and the ability to mount an antibody response to the infection was impaired, suggesting that the poor antibody response may contribute to the liability of HIV-infected patients to have PCP.

AIDS-Related Opportunistic Infections↗

PubMed1998

Viremia in chronic hepatitis C patients evaluated by the Amplicor RT-PCR, a nested RT-PCR, and transaminase levels.

A commercially available kit, Amplicor, was compared with a locally developed nested reverse-transcriptase (RT) PCR for qualitative detection of HCV-RNA. Sixty-one serum samples from sixty-one patients with liver disease, and 60 samples from 60 hemophiliacs without symptoms, but known to have been heavily exposed to hepatitis C virus, were investigated. There was a high degree of concordance between the two diagnostic tests (97%), the Amplicor kit being slightly more sensitive than the in-house PCR, when evaluated using serial dilutions of samples showing discrepant results. The relationship between viremia and abnormal ALT levels was studied in the two groups of patients. Among those with chronic liver disease, 8.3% of patients with viremia had normal ALT levels, whereas transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT as being a poor marker of ongoing viral replication.

Adolescent↗

PubMed1995

Decreased activation of the respiratory burst in neutrophils from AIDS patients with previous Pneumocystis carinii pneumonia.

Neutrophils from human immunodeficiency virus (HIV)-negative blood donors, asymptomatic HIV-positive patients, AIDS patients with previous Pneumocystis carinii pneumonia (PCP), and AIDS patients without previous PCP were compared for their ability to activate the respiratory burst, measured as luminol-amplified chemiluminescence. P. carinii, Staphylococcus aureus, phorbol-12-myristate-13-acetate, and FMLP were used to stimulate the neutrophils. When stimulated with P. carinii, neutrophils from PCP patients had a significantly lower response than the other groups, whereas no difference was found when S aureus was used. A somewhat but not significantly lower response to P. carinii was also seen in non-PCP patients compared with HIV-negative donors. Priming of the neutrophils with recombinant granulocyte colony-stimulating factor (G-CSF) or recombinant human granulocyte-macrophage (GM)-CSF corrected this defect. A similar effect of these cytokines was seen on phagocytosis, whereas the chemiluminescence in unprimed cells did not correlate with phagocytosis.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Pneumocystis carinii-induced activation of the respiratory burst in human monocytes and macrophages.

Human monocytes and monocyte-derived macrophages were studied for their ability to phagocytose Pneumocystis carinii and produce superoxide (O2-) during the process. One x 10(6) freshly isolated monocytes, incubated with 0.1-3.75 x 10(6) P. carinii cysts, increased O2- production in a dose-related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O2- production significantly above the response obtained by lung tissue from rats (10.7 and 4.9 versus 3.0 fmol/cell per 90 min). The difference between pneumocysts opsonized in untreated versus complement-depleted serum was not significant (10.7 versus 12.6 fmol/cell per 90 min). Monocyte-derived macrophages also activated the respiratory burst when stimulated with pneumocysts, and this effect could be significantly increased, from 4.2 to 8.8 fmol/cell per 90 min, when cells were primed with interferon-gamma (IFN-gamma). Cells primed with IL-3 also increased O2- production, though to a lesser extent. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) had only a small effect on the respiratory burst in cells stimulated with P. carinii. Priming with IFN-gamma increased the rate of phagocytosis in macrophages. After incubation for 90 min or more, however, the percentage of cells with phagocytic vacuoles was only slightly higher in IFN-gamma-primed cells. When examined by electron microscopy (EM), most vacuoles contained partially or totally degraded pneumocysts. In conclusion, we have demonstrated the ability of monocytes and monocyte-derived macrophages to ingest and degrade pneumocysts, activating the respiratory burst during the process.

Animals↗

PubMed1994

Local antibodies against Pneumocystis carinii in bronchoalveolar lavage fluid.

Pneumocystis carinii pneumonia (PCP) is a frequent cause of pneumonia among human immunodeficiency virus (HIV)-infected patients. Little is known, however, about the role played by humoral immunity to control the infection. This study was undertaken to elucidate the role played by local antibodies. Bronchoalveolar lavage (BAL) fluids from 18 acquired immune deficiency syndrome (AIDS) patients with PCP, 20 HIV-antibody positive patients without PCP, and 20 lung cancer patients were examined for antibodies against P. carinii by the indirect immunofluorescence method. The ratio of albumin concentration in BAL fluid to serum was used to standardize the lavage fluids. Immunoglobulin G (IgG) antibodies against P. carinii occurred less frequently, and immunoglobulin M (IgM) antibodies more frequently, in PCP patients than in other groups. Immunoglobulin A (IgA) antibodies against pneumocysts were found with the same frequency in all three groups, although the median titre was lower among HIV-antibody positive patients without PCP, compared with the other groups. When indexed (antibody titre in BAL fluid x albumin concentration in serum/antibody titre in serum x albumin concentration in BAL fluid) to express locally produced antibodies, IgG indices were significantly higher in HIV-infected patients without PCP, whereas IgM and IgA indices were significantly higher in PCP patients. These findings suggest that the local IgG response is impaired in patients with PCP, whereas the local IgA and, to some extent, the IgM responses are preserved.

AIDS-Related Opportunistic Infections↗

PubMed1993

Phagocytosis and stimulation of the respiratory burst in neutrophils by Pneumocystis carinii.

Phagocytosis and superoxide production of neutrophils stimulated with Pneumocystis carinii were studied using P. carinii obtained from rats and neutrophils and serum from healthy blood donors. Superoxide generation increased in a dose-related way to the number of pneumocysts added and was significantly higher when the parasites were opsonized. The use of heat-inactivated serum for opsonization reduced superoxide production somewhat, but not significantly. Preincubation of neutrophils with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) increased superoxide production in neutrophils stimulated with pneumocysts from 7.0 to 9.6 fmol/cell/20 min; however, the production in unstimulated cells increased by the same amount. Activation of the respiratory burst was paralleled by phagocytosis, and very few phagocytic vacuoles were found in neutrophils stimulated with unopsonized pneumocysts. By electron microscopy, various stages of cyst degradation were seen.

Animals↗

PubMed1993

The C-reactive protein responses in HIV-infected patients with pneumonia.

The acute phase C-reactive protein (CRP) was measured in serum of HIV-infected patients suffering from Pneumocystis carinii pneumonia (PCP) (32 patients), bacterial pneumonia (10 patients), and in 19 immunocompetent patients with bacterial pneumonia. The HIV-infected patients with bacterial pneumonia had a significantly lower CRP level than the immunocompetent patients (50% versus 95% had an s-CRP level > 80 mg/l). No significant difference was found in the CRP response to P. carinii or bacteria in HIV-infected patients with pneumonia due to these microorganisms (20% versus 50% had s-CRP > 80 mg/l). In the group of PCP patients, a significantly lower CRP level was found in those with CD4 positive lymphocyte counts below 50 x 10(6)/l. There was no correlation between the CRP response and the severity of the PCP as estimated by the degree of hypoxia. We conclude that the CRP level cannot be used to discriminate between PCP and bacterial pneumonia in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Effects of serotonergic and anticholinergic drugs in haloperidol-induced dystonia in Cebus monkeys.

In rodents, serotonin (5-HT) antagonists counteract behavioral and biochemical effects of neuroleptic drugs. Therefore, we have studied the effect of different 5-HT drugs and one anticholinergic drug in acute dystonia in five cebus monkeys chronically treated with haloperidol. Acute dystonia induced by subcutaneous injections of haloperidol was slightly reduced by the 5-HT antagonist methysergide (4.0 mg/kg), while mianserin, ketanserin, and ritanserin (R 55 667; a new selective and potent 5-HT receptor blocker) had no effect. This was contrasted by the marked antidystonic effect of the anticholinergic drug biperiden (0.05-1.0 mg/kg). The 5-HT agonist citalopram, a specific 5-HT uptake inhibitor, had no significant effect. It is concluded that 5-HT antagonists have no useful effect in neuroleptic-induced dystonia.

Animals↗

PubMed1985

Paroxetine in the treatment of depression--a randomized comparison with amitriptyline.

Paroxetine is a new antidepressant drug with potent serotonin (5HT) uptake inhibitory properties. In this double-blind comparative study, the antidepressant effect of paroxetine and amitriptyline has been compared in 44 patients with depressive illnesses of an endogenous nature. Each drug was given for 6 weeks. The 17-item Hamilton Depression Scale was used to measure the antidepressant effect. Reported events were assessed applying a 22-item check list. Non-parametric statistical analyses were applied in the evaluation of treatment outcome for the 30 patients who completed the study. The results showed no significant differences in overall antidepressant efficacy between paroxetine and amitriptyline and that paroxetine displayed significantly fewer instances of dry mouth and orthostatic dizziness than amitriptyline. No obvious relationship was demonstrated between the plasma levels of the drugs and their clinical effects.

Adult↗

PubMed1983

Dexamethasone suppression test and TRH test in endogenous depression.

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.

Adolescent↗

PubMed1981

Termination of insulin-induced hexose transport in adipocytes.

The hexose transport of insulin-pretreated (80 pM) adipocytes remained elevated for at least 45 min when the cells were depleted of ATP by treatment with dinitrophenol. On the other hand, the half-time of deactivation of hexose transport in insulin-pretreated cells was of the same magnitude as that of dissociation of receptor-bound insulin both in the absence and presence of glucose (about 8 min). Thus, a high ATP-level, but not ongoing glucose metabolism appears to be important for termination of the insulin effect shortly after dissociation of insulin from its receptor.

Adenosine Triphosphate↗

PubMed1981

Analysis of information in indicant-patterns.

Different patterns of information may lead to identical diagnostic conclusions, but it remains uncertain whether such patterns will have the same validity towards other criteria, e.g. choice of treatment. A procedure for selection of optimal patterns of data and analysis of their validity towards different criteria is described. It is founded on Bayes' methodology and characterized by a continuous correction for redundancy between indicants. Permissible patterns/syndromes are formulated and evaluated in a consistent way.

Diagnosis, Computer-Assisted↗

PubMed1981

Evaluation of data-base.

The records of 421 psychiatric patients were analysed by a consistent method, allowing an optimal use of indicant-patterns. It was assumed that such a procedure would give a satisfactory predictive capacity, even for operational criteria as for example choice of treatment, duration of stay in hospital, or a global evaluation of outcome. The study demonstrates, however, that fundamental changes in the data-base are necessary. Problems of reliability, validity, sensitivity and specificity are discussed and some suggestions are offered for the future improvement of psychiatric data-bases.

Diagnosis, Computer-Assisted↗

PubMed1980

Insulin binding and hexose transport in rat adipocytes. Relation to cell size.

Insulin binding, initial velocity of [14C]methylglucose transport, uptake of [14C]deoxyglucose and conversion of [U-14C]glucose to CO2, glyceride-glycerol and fatty acids were measured at 37 degrees C in adipocytes from rats of different weights (135-450 g) and therefore with different mean cell volumes (53-389 pl). Insulin binding per cell increased with increasing cell size and binding was 2.3 times higher in the largest cells than in the smallest cells with tracer alone. The difference was largely accounted for by an increase in the apparent affinity. Influx of methylglucose per cell increased with increasing cell size in the absence of insulin and remained constant as a function of cell size in its presence. The effect of insulin ranged from 11 fold in small cells to 3.5 fold in large cells. The rat of conversion of [U-14C]glucose to CO2 and lipids was about half of the rate of methylglucose transport under all conditions. In contrast, the uptake of deoxyglucose in insulin-stimulated cells decreased markedly with increasing cell size. Increasing cell size caused a small decrease in sensitivity which could be explained by a smaller amont of insulin bound per unit surface area. The results show that increasing cell size/animal weight causes changes in insulin binding which may explain changes in sensitivity. In addition, the hexose transport system is modified in a way which is not explained by changes in insulin binding. Finally, changes in deoxyglucose uptake with cell size do not parallel changes in methylglucose transport.

Adipose Tissue↗