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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 145 records · Page 8Linked to original sources

Effect of ranitidine on soluble interleukin 2 receptors and CD8 molecules in surgical patients.

The effect of perioperative immunomodulation with the H2-receptor antagonist ranitidine on postoperative changes in soluble interleukin (IL) 2 receptor and soluble CD8 levels was assessed in 24 patients undergoing major elective abdominal surgery. Eleven patients were randomized to receive intravenous ranitidine 100 mg twice daily for 4 days from skin incision, followed by oral ranitidine 150 mg twice daily for a further 5 days; 13 control patients received no ranitidine. Routine blood analysis, clinical data, duration of surgery, anaesthesia, antibiotic prophylaxis and perioperative blood transfusion were similar in the two groups. Serum concentrations of soluble IL-2 receptor and CD8 were measured before operation (day 0) and in the morning of postoperative days 1, 3 and 9 using commercial enzyme-linked immunosorbent assay kits. In patients treated with ranitidine, the serum level of soluble IL-2 receptor increased from day 0 to day 9 (P < 0.01); in control patients it decreased from day 0 to day 1, did not change significantly by day 3 and increased by day 9. The change from day 0 to day 1 was significantly different between the two groups (P < 0.01). Five of the 13 control patients developed postoperative infectious complications. No significant differences were shown in soluble CD8 concentration during the postoperative period. The postoperative change in soluble IL-2 receptor level may reflect lymphocyte activation status; ranitidine appears to promote activation of mainly CD4-positive lymphocytes since serum levels of CD8 were unchanged. Ranitidine may, therefore, improve immune function during major surgery.

Abdomen↗

Neutrophil activation by Helicobacter pylori lipopolysaccharides.

Helicobacter pylori-induced release of toxic substances by neutrophils could be of potential importance in the pathogenesis of gastroduodenal inflammatory diseases. Lipopolysaccharide (LPS) has the ability to induce neutrophil activation at very low concentrations. Neutrophil oxidative metabolism and enzyme release were assessed after stimulation of neutrophils with various preparations of LPS from H. pylori and compared with that obtained with Salmonella typhimurium LPS. No direct activation of neutrophils by LPS was observed. Preincubation with LPS showed a significant priming for increased activity on subsequent stimulation, particularly with rough-form LPS. The potency of H. pylori LPS was 10-fold lower than that of S. typhimurium LPS, probably reflecting the unique biochemical structure of H. pylori LPS. Chronic low-grade stimulation by H. pylori LPS in the gastric mucosa may render neutrophils primed for the excessive release of detrimental substances into the tissue on stimulation by other mediators.

Adult↗

Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers.

The aim of the present study was to investigate whether tinzaparin sodium (a low-molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c., 175 anti-Xa IU tinzaparin/kg b.w. s.c., or 1 ml of saline s.c. PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0.5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-IIa activities were seen following i.v. tinzaparin. In the s.c. groups 60-65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65-75%), anti-IIa activity (55%) and aPTT activity (35-45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy.

Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance spectroscopy (MRS). Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. Spectroscopic examinations were performed with the stimulated echo acquisition mode (STEAM) method on a 1.5 T clinical whole-body imaging unit. A cubic volume of interest (VOI) was selected in the bone marrow of the left iliac bone. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)/l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur. In conclusion, the non-invasive MRS method may be a useful and reliable in vivo examination for expansion of haemopoiesis and a correspondent reduction of fat tissue in bone marrow after priming with recombinant human haemopoietic growth factors.

Adult↗

Circulating monocytes are activated in newly diagnosed type 1 diabetes mellitus patients.

Investigations in the BB rat and the non-obese diabetic (NOD) mouse have provided substantial evidence for the involvement of the monocyte/macrophage system in the development of type 1 diabetes mellitus. However, it is not known whether monocytes play the same role in the pathogenesis of human type 1 diabetes. We investigated this problem in a longitudinal study of 29 recent-onset type 1 diabetes mellitus patients. Monocyte chemotaxis, phagocytosis and superoxide production as well as metabolic and haematological parameters were studied immediately after diagnosis and 6 months later. At diagnosis the patients had activated casein and C5a chemotaxis (casein 70 +/- 9 versus 150 +/- 5 (mean +/- s.e.m.), P < 0.001; C5a 137 +/- 10 versus 158 +/- 5, P < 0.05 (activation immobilizes monocytes, reducing the measured values)), and activated superoxide production (3.6 +/- 0.3 versus 3.0 +/- 0.3, P < 0.05). After 6 months casein chemotaxis (115 +/- 16 versus 150 +/- 5, P < 0.05) and Candida phagocytosis (3.3 +/- 0.1 versus 2.8 +/- 0.2, P < 0.001) were still activated. There was no correlation with other clinical or paraclinical parameters. We conclude that the circulating monocytes in newly diagnosed type 1 diabetes patients are activated. It is reasonable to expect that monocytes at the local site of inflammation in pancreas are even further activated. This could play a pathogenic role in beta cell destruction.

Adult↗

Metabolic remission with octreotide in patients with insulinoma.

OBJECTIVES: The efficacy of octreotide was studied in a group of patients with biochemical evidence of insulinoma. DESIGN: A phase-II study. SETTING: A university department of internal medicine. SUBJECTS: Seven patients with biochemical evidence of insulinoma and without metastatic lesions. INTERVENTION: Daily treatment with octreotide, a somatostatin analogue, mainly within the dosage of 100-300 micrograms day-1. The treatment was continued in patients with biochemical evidence of response or until surgery was undertaken. MAIN OUTCOME: Five patients avoided hypoglycaemic symptoms and had normalization of blood glucose values for a median of 15+ months (range 0.2-54 months). Two did not improve metabolically. The treatment was well tolerated and had no deleterious effects on blood glucose regulation. CONCLUSION: Octreotide seems to be a promising treatment for many of the patients with insulinoma who are not suitable for surgery.

Adult↗

Immunoglobulin preparations for intravenous administration. A review of their biologic activities and comparison of various preparation methods.

Substitution therapy with human immunoglobulin preparations is well established in disorders of primary or secondary deficiencies of humoral immunity. However, modifications of the immunoglobulins are required to achieve tolerance for the preferred intravenous route of administration. Several procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc-receptor function, are subject to alterations during the preparation. The best preservation of such activity, when assessed in vitro, is obtained with polyethylene glycol precipitation or DEAE-Sephadex fractionation, whereas enzymatic or chemical treatment can potentially reduce the biologic activity. It is recommended that immunoglobulin preparations be evaluated in vitro for intact biologic function before being given to immunodeficient patients.

Complement Fixation Tests↗

Occupational exposure to isothiazolinones. A study based on a product register.

A national data base on chemical products (the Danish Product Register (PROBAS)) was searched in order to survey occupational exposure to isothiazolinones. 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothiazolin+ ++-3-one(MCI/MI) was registered in 550 products, 1,2-benzisothiazolin-3-one(BIT) in 156 products and 2-n-octyl-4-isothiazolin-3-one in 16 products. For the MCI/MI-containing products, of which 343 had information on concentration, 64% of the products contained above or equal to 0.001% (10 ppm) MCI/MI. Main product categories were paints, hair shampoos, skin care products, and cleaning agents. For BIT-containing products, of which 139 had information on concentration, 54% of the products contained above or equal to 0.01% (100 ppm) BIT. Main product categories were cleaning agents, polishes, and paints. Only a few products were registered with content of 2-n-octyl-4-isothiazolin-3-one and these were not studied further. The dermatological literature has often focused on isothiazolinones in cosmetics as the source of allergy. The present study showed that attention should also be paid to occupational exposure, as isothiazolinones occur in many industrial product categories.

Databases, Factual↗

Oral candidiasis and immune status of HIV-infected patients.

A total of 84 HIV-infected homosexual men having either normal oral mucosa (NOM), erythematous candidiasis (EC) or pseudomembranous candidiasis (PsC) were included in the study. The patients were evaluated by median number of peripheral CD4+ cells, CD8+ cells and by lymphocyte function assessed by poke-weed mitogen test. There was a significant difference between CD4+ counts among patients with the two subtypes of candidiasis (95% CI of median difference: 10-240/mm3; P = 0.03), but not for pokeweed mitogen response. Survival analysis showed that after 2 y there was no significant difference in development of AIDS between patients with EC and PsC (P = 0.29). If patients with both types of oral candidiasis were pooled and compared with patients with NOM, a significant difference in development of AIDS was found (P = 0.04). It is concluded that HIV-infected patients with oral candidiasis of any subtype (EC or PsC) are significantly more immune suppressed and show a faster development of AIDS than HIV-infected patients with NOM. However, in this cohort, EC and PsC are of equal importance as predictors for immune suppression and AIDS development.

Acquired Immunodeficiency Syndrome↗

Chronic fatigue syndrome--a controlled cross sectional study.

OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS). METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells. RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups. CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained.

Adolescent↗

[Changes of sexual behavior among Danish homo/bisexual men under the impact of HIV/AIDS epidemic].

In October 1991, 1.567 gay/bisexual men throughout Denmark returned an anonymous questionnaire enclosed in the magazine of the National Gay and Lesbian Association. Most were younger, well educated men living in the Copenhagen area. 76% had been tested for HIV, 15% were infected. As in 1988, the median number of partners in 1991 was 2-5. Eighty-two percent of the sexually active men engaged in anal sex, of these half used condoms consistently. Anal sex was practised more with steady partners and condom use was more common with casual partners. One out of eight had engaged in unprotected anal intercourse with a partner with discordant HIV-serostatus, down from one in three in 1988. It is concluded, that Danish gay men have not further limited their sexual life during the later years. The majority of the respondents have increased sexual safety, but risky sex still prevails among a substantial minority, and safe sex campaigns should continue.

Acquired Immunodeficiency Syndrome↗

Characterization of anti-HLA class II monoclonal antibody LGII-612.14 reacting with formalin fixed tissues.

mAb LGII-612.14 derived from a BALB/c mouse immunized with interferon-gamma (IFN-gamma) treated cultured human B lymphoid cells LG-2 has been shown with serological and immunochemical assays to recognize a monomorphic determinant expressed on the beta chain of HLA-DR, -DQ and -DP antigens. The linear nature of the determinant, which is likely to be formed by residues 19-25, is indicated by the reactivity of mAb LGII-612.14 with HLA-DR, -DQ and -DP beta chains purified by electrophoresis in presence of SDS. An unusual characteristic of mAb LGII-612.14 is its reactivity with fixed tissue sections. The intensity of staining is affected by the incubation temperature, the incubation time and the fixative used. Maximal intensity of staining of formalin fixed, paraffin embedded tissue sections required an incubation time of 16 h. The intensity of staining of paraffin embedded tissues initially fixed with Bouin's solution, formalin or ethanol was similar to that of frozen tissue sections and stronger than that of tissues fixed with B5 solution. No staining was detected of paraffin embedded tissues fixed with glutaraldehyde or Zenker's solution. Comparison of the staining patterns with mAb LGII-612.14 of frozen and fixed tissue sections showed that the latter substrates provide a superior detail of tissue architecture and cellular morphology without significant loss of sensitivity. Furthermore, comparison of the characteristics of mAb LGII-612.14 with the few previously published anti-HLA class II mAb reacting with fixed tissues indicates that mAb LGII-612.14 stains formalin fixed, paraffin embedded tissues, while mAb 910D7 and TAL-1B5 stain tissues fixed with less commonly used fixatives. Furthermore, mAb LGII-612.14 is likely to yield more sensitive staining results than anti-HLA-DR, -DQ and -DP mAb KUL/05. The present results indicate that mAb LGII-612.14 represents a useful probe to apply immunohistochemical techniques to the analysis of the distribution of HLA class II antigens in fixed tissues. This will greatly facilitate the use of readily available collections of fixed tissue specimens in retrospective studies to assess the clinical significance of changes in HLA class II antigen expression which occur in various disease states.

Animals↗