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Biomedical subjects

S Møller

Publications and source records attributed to S Møller.

At least 127 records · Page 7Linked to original sources

Antigen specific in vitro activity of lymphocyte subpopulations from Mantoux positive and negative subjects assessed by lymphocyte proliferation assay.

A micromethod for the lymphocyte proliferative assay and multifactorial analysis of stimulation indices classified according to subjects, lymphocyte combinations and antigens was used to elucidate deficient Mantoux (Mx) reactions in BCG-vaccinated subjects. It was possible to group each of the factors so that interactions between the two latter factors were not present within but only between groups. Comparisons between the subject groups showed a clear association between results of this in vitro test with PPD antigen and the Mx test carried out with 1 TU. The in vitro test had the advantage of being more sensitive and of not introducing the immune reactions occasionally seen with the Mx test. Thymus-processed lymphocytes were the cells responsible with functions both as effector and regulator cells, B lymphocytes had only regulatory properties.

Analysis of Variance↗

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule.

Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concentrations of antibiotics was smaller in the same child throughout the treatment course, but greater between the infants. The 95% limits for the serum concentrations of antibiotics were, however, nearly the same in the two treatment groups, and the use of a dosage schedule is therefore recommended. Serum gentamicin concentration should be assayed about 3 half lives (18 hours) after beginning the treatment, and dosage adjustment be made if the serum gentamicin concentration is outside 3-5 micrograms/ml.

Ampicillin↗

In vivo and in vitro boosting effects of tuberculin skin tests in guinea-pigs immunized with living BCG or with killed Mycobacterium tuberculosis.

Eight weeks after the onset of immunization with living BCG vaccine or with heat-killed, dried Mycobacterium tuberculosis in paraffin oil (TB), guinea-pigs were skin tested with small doses of tuberculin PPD. Three weeks later the effect of these tests on skin reactions and on lymphocyte transformation (LT) responses of lymph node lymphocytes (LNL) or peripheral blood lymphocytes (PBL) was estimated by a comparison with non-tested groups. For both immunogens, the skin test after 8 weeks significantly enhanced skin reactions, particularly to low tuberculin doses. In the BCG-vaccinated guinea-pigs the LT responses of both cell types were significantly enhanced by the skin test after 8 weeks, whereas the LT responses from the TB-immunized guinea-pigs were not affected. Therefore, in the planning and interpretation of in vitro tests of cellular immunity, possible effects from previously applied skin tests should be taken into consideration.

Animals↗

Leucocyte migration inhibition in vitro with inhibitors of aspartic and sulphhydryl proteinases.

The human leucocyte migration in the leucocyte migration under agarose technique ( LMAT ) was investigated with specific inhibitors of aspartic, sulphhydryl , metallo- and serine proteinases. The general aspartic proteinase inhibitor pepstatin and the highly specific competitive cathepsin D inhibitor, N-gly-glu-gly-phe-leu-gly-D-phe-leu suppressed leucocyte migration at concentrations of 20-200 mumol/l and 30-59 mumol/l, respectively. The suphhydryl enzyme inactivator, N-ethylmaleimide suppressed leucocyte migration at concentrations of 100-200 mumol/l. Several inhibitors of serine- and metallo enzymes were tested, but none had any effect on leucocyte mobility, although the metal binding agent 8-hydroxyquinoline was strongly inhibitory to cell migration, the significance of which is discussed.

Aprotinin↗

Studies on the development of tuberculin sensitivity in immunized guinea pigs with demonstration of a close relationship between results of skin tests and the lymphocyte transformation technique.

The development of tuberculin sensitivity in groups of guinea pigs immunized with living BCG vaccine or with heat-killed Mycobacterium tuberculosis suspended in oil (TB) was measured by skin tests and lymphocyte transformation (LT) tests with tuberculin PPD. LT tests on lymphocytes from peripheral blood (PBL) and lymph nodes (LNL) and skin tests were carried out on different groups of guinea pigs for 1 year following immunization. Three ways of expressing the LT results were considered, i.e. as stimulation index, delta cpm and uncorrected cpm values. Since neither of the first two methods were equally applicable to all of the data, we decided to express the data as geometric means of cpm values for stimulated and control cultures, respectively. For both immunogens the sensitivity measured by PBL LT and skin tests showed a closely parallel development; LNL reactivity appeared earlier and remained at a higher level than PBL reactivity. Antibody levels in the guinea pigs were measured using a radioimmunoassay technique, were found to be dependent on the immunization period and not correlated to the cellular immunity.

Animals↗

Effect of 2-mercaptoethanol and mycostatin on guinea pig lymphocyte transformation: interpretation of results depends on the method of calculation.

The stimulating effects of 2-mercaptoethanol (2-ME) reported in murine cell cultures were confirmed for guinea pig lymphocyte transformation (LT). 2-ME was mitogenic for peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) and enhanced PPD-induced LT. The effect on LNL was dependent on the magnitude of the response of non-2-ME treated cultures. The 2-ME effect on PPD-stimulated LNL was reversed when stimulation index (SI) replaced the delta cpm estimate. Mycostatin (MYC) inhibited the blastogenic response of PBL control cultures, whereas its effect on LNL control cultures varied. The interpretation of the effect of MYC on PPD-stimulated cultures was dependent on the use of the delta cpm or SI estimates. The interpretation of LT experiments is therefore highly dependent on whether delta cpm or SI is used for expression of results. Analysis of effects on control and stimulated cultures should precede the addition of 2-ME or MYC to cultures for LT.

Animals↗

Ceftazidime treatment of chronic Pseudomonas aeruginosa respiratory tract infection in cystic fibrosis.

Two open randomized cross-over studies were undertaken comparing ceftazidime to tobramycin and ceftazidime to tobramycin plus carbenicillin in 13 and 15 cystic fibrosis (CF) patients, respectively, with chronic bronchopulmonary Pseudomonas aeruginosa infection. The difference in lung function improvement was statistically better in terms of FEV1 and FVC for the ceftazidime group in the study versus tobramycin plus carbenicillin. Patients receiving ceftazidime showed a tendency for a greater long-term benefit in lung function as measured at 1 and 2 months after treatment than patients receiving the other antibiotics. Development of resistance against both ceftazidime and carbenicillin was seen regularly and was not prevented by combination therapy with tobramycin. No resistance developed when tobramycin was used as monotherapy. Serum concentration curves for ceftazidime fitted a two compartment first order open model in CF patients and showed a distribution volume of 40% of the body weight and a final serum half-life of 1.8 h. One case of Type III hypersensitivity reaction was seen during ceftazidime treatment. Ceftazidime seems to be an effective and safe antibiotic in the treatment of Ps. aeruginosa bronchopulmonary infection in CF patients, although these bacteria could not be eradicated.

Adolescent↗

Kinetics and dose calculations of ampicillin and gentamicin given as continuous intravenous infusion during parenteral nutrition in 88 newborn infants.

Ampicillin and gentamicin were administered continuously intravenously to 88 newborn infants using individually calculated dosages. For infants with a mean value of plasma clearance of the antibiotics, it was calculated that the serum ampicillin and gentamicin concentrations would be between 35-55 and 3-5 micrograms/ml, respectively, using the dosages for intermittent treatment. These dosages are therefore recommended as fixed dosages for continuous intravenous infusion initiated by a bolus dosage. Serum gentamicin concentration should be assayed about three half-lives after start of infusion and the dosage adjusted for values outside 3-5 micrograms/ml.

Ampicillin↗

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants.

Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours respectively, and the 95% limits for the serum concentrations were 11-133 and 1.3-7.4 micrograms/ml. The treatment results were at least as good as with intermittent intramuscular or intravenous administration. This new mode of giving antibiotics is less painful to the babies and easier for the nurses.

Ampicillin↗

Experimental endocarditis in rabbits. 5. Results of long-term penicillin or streptomycin treatment of streptococcus faecalis endocarditis and the effect of long-term exposure of healthy rabbits to the same drugs.

A previously described model of experimental Streptococcus faecalis endocarditis in rabbits without an indwelling catheter during the infectious processes was used to study the effect of long-term treatment with antibiotics. Groups of animals infected with six different strains were treated for four weeks and the following parameters were determined: survival rate, bacterial concentration in blood and vegetations, signs at autopsy indicating congestive heart failure. Before the therapeutic experiments, the tolerance of the rabbit to long-term exposure of the drugs penicillin and streptomycin was considered in a group of non-infected animals. Two out of 20 rabbits died with enteritis during the penicillin exposure, and a general weight reduction was observed. Streptomycin was apparently completely harmless. There was no therapeutic effect of streptomycin on S. faecalis endocarditis due to strains all designated resistant to streptomycin by MIC, except in rabbits infected with a strain, which showed partial susceptibility to the drug by IC50. Regardless of the therapeutic effect, evidence was obtained for rapid development of increased resistance of the infecting strains towards streptomycin. After long-term treatment with penicillin in either low or high dose some of the animals survived and the valves were sterilized in 37% of the animals after low-dose and in 39% after high-dose. It was observed that congestive heart failure occurred with the greatest frequency and intensity after infection with proteolytic strains.

Animals↗

Statistical evaluation of the lymphocyte proliferation assay with non-stimulated cultures.

A micromethod for the lymphoproliferative assay has been evaluated statistically with non-stimulated human lymphocyte combinations. Different variance components were estimated by means of a hierarchical analysis of variance. Instead of using an arbitrary value for a significant difference between stimulated and non-stimulated cultures, the value can be calculated on the basis of the components of variance in the experimental design. The method disclosed systematic differences between the values of control cultures depending on the lymphocyte combinations and groups of persons examined, which underlines that every experiment should always contain non-stimulated cultures. Further, cell-cell cooperation and differences in spontaneous DNA synthesis within individual lymphocyte populations could be demonstrated.

Analysis of Variance↗

Experimental endocarditis in rabbits. 4. Experiments with Serratia marcescens: on the significance of serum susceptibility and proteolytic capacity of the strains and the influence of an indwelling catheter.

In order to investigate the course of Serratia marcescens endocarditis in groups of rabbits with and without an indwelling catheter, 130 rabbits were pretreated to produce left-sided endocarditis. Three clinical isolates of S. marcescens were used to infect the rabbits, i.e. CDC O13 (serum sensitive, proteolytic), SM 104 (serum resistant, proteolytic) and SM 55 (highly serum resistant, non-proteolytic). Ten rabbits with an indwelling catheter were challenged with CDC O13 and none of them died or showed evidence of endocarditis 28 days later. In groups of rabbits with indwelling catheters which were challenged with SM 104 or SM 55 there was a high incidence of endocarditis (19/20, 18/20, respectively), while groups without catheters inoculated with the same strains had a lower incidence (5/20, 15/20, respectively). In contrast to earlier observations with Streptococcus faecalis, the clinical and pathological data were not significantly influenced by the presence or absence of proteolytic capacity of the infecting strains. The results indicate that the ability of S. marcescens to establish endocarditis depends significantly on the degree of serum resistance of the strains. This difference was only demonstrable in experiments without an indwelling catheter during the infection period. The distrurbing influence of an indwelling catheter is discussed, and it is concluded that experimental models using indwelling catheters are inappropriate for studies on the pathophysiology of endocarditis.

Animals↗

Experimental endocarditis in rabbits. 3. Significance of the proteolytic capacity of the infecting strains of Streptococcus faecalis.

Insertion of a polyethylene catheter into the left ventricle of the heart was used for regular establishment of sterile endocarditis, and bacterial endocarditis was established by injection of approximately 10(8) Streptococcus faecalis into the blood stream at the same time as removal of the catheter which had been in place for 3 days. 100 out of 102 rabbits died spontaneously of bacterial endocarditis. Evidence is produced that the host-parasite interaction is influenced by the proteolytic property of S. faecalis in this experimental model. Two distinct types of clinical course are described: 1) A predominantly acute and damaging illness, characterized by a high level of bacteraemia, small amounts of soft, friable vegetations in the left side of the heart, high frequency of kidney infarcts and shorter survival time in rabbits infected with proteolytic strains. 2) A relatively subacute illness, characterized by a lower level of bacteraemia, large, hard, non-friable vegetations on the aortic valves, less pronounced destructive changes in the substance of valve leaflets, relatively lower frequency of kidney infarcts and longer survival time in rabbits infected with non-proteolytic strains. The results suggest that proteolytic strains of S. faecalis cause partial dissolution of the vegetations resulting in a more severe clinical picture.

Animals↗

The epidemiology of febrile reactions in haemodialysis.

Febrile reactions were studied in 2 000 consecutive haemodialyses performed in 85 patients. A number of 219 febrile reactions were registered in 49 patients (11%). The overall month-to-month incidence showed little variation. Febrile reactions were not distributed randomly among the patients; those with respiratory tract infection experienced more febrile reactions during periods with infection than during periods without. Similarly, the incidence was higher in patients with than without chronic urinary tract infection. A low incidence was registered both in patients under 40 years of age and in patients having had more than 100 dialyses at the beginning of the observation period. The frequency was the same whether single-pass or recirculating single-pass monitors had been used, and it was not influenced by blood transfusions during dialysis. Thus, our analysis leads to the conclusion that the majority of the febrile reactions registered among the present patients were determined by endogenous factors such as infection, while exogenous factors such as dialysate bacteria and pyrogens seem to have played only a minor role.

Adolescent↗