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Biomedical subjects

P Christensen

Publications and source records attributed to P Christensen.

At least 19 recordsLinked to original sources
PubMed1992

Prevention of excess neonatal morbidity associated with group B streptococci by vaginal chlorhexidine disinfection during labour. The Swedish Chlorhexidine Study Group.

Streptococcus agalactiae transmitted to infants from the vagina during birth is an important cause of invasive neonatal infection. We have done a prospective, randomised, double-blind, placebo-controlled, multi-centre study of chlorhexidine prophylaxis to prevent neonatal disease due to vaginal transmission of S agalactiae. On arrival in the delivery room, swabs were taken for culture from the vaginas of 4483 women who were expecting a full-term single birth. Vaginal flushing was then done with either 60 ml chlorhexidine diacetate (2 g/l) (2238 women) or saline placebo (2245) and this procedure was repeated every 6 h until delivery. The rate of admission of babies to special-care neonatal units within 48 h of delivery was the primary end point. For babies born to placebo-treated women, maternal carriage of S agalactiae was associated with a significant increase in the rate of admission compared with non-colonised mothers (5.4 vs 2.4%; RR 2.31, 95% CI 1.39-3.86; p = 0.002). Chlorhexidine reduced the admission rate for infants born of carrier mothers to 2.8% (RR 1.95, 95% CI 0.94-4.03), and for infants born to all mothers to 2.0% (RR 1.48, 95% CI 1.01-2.16; p = 0.04). Maternal S agalactiae colonisation is associated with excess early neonatal morbidity, apparently related to aspiration of the organism, that can be reduced with chlorhexidine disinfection of the vagina during labour.

Administration, Intravaginal↗
PubMed1992

Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers.

The sedative and cortisol suppressing properties of oxazepam (45 and 60 mg) and nitrazepam (10 and 15 mg) were examined in eight healthy male subjects. The most clear differences between oxazepam and nitrazepam were those seen with respect to the time course and until maximal effect (Tmax) of the different measurements. Nitrazepam showed maximal sedation after 1 h, maximal benzodiazepine level (RRA), and reaction time prolongation after 2 h, and maximal cortisol suppression after 3 h. Oxazepam showed maximal sedation after 2 h, maximal benzodiazepine levels, reaction time prolongation and cortisol suppression after 3 h. After administration of oxazepam (both doses) a transient return to baseline levels of cortisol was demonstrated. Whereas the degree of sedation correlated significantly within drug groups with the concurrent benzodiazepine levels, the Tmax of sedation was recorded 1 h earlier than the peak blood concentration (RRA) for both nitrazepam and oxazepam. The time course for cortisol suppression for the two compounds differed clearly from the other measurements and was not related to the peak blood concentration.

Affect↗
PubMed1992

A factor secreted by a human pulmonary alveolar epithelial-like cell line blocks T-cell proliferation between G1 and S phase.

Because the pulmonary alveolar space is both the site of gas exchange for respiration and a portal of entry for foreign antigen, immunologic interactions within that space must be meticulously controlled. Alveolar epithelial cells are ideally situated to play a role in immune regulation within the alveolar space. We have used A549 cells, a cell line that is derived from a human alveolar cell carcinoma and that has been used as a model for alveolar type II epithelial cells, to examine the potential role of alveolar epithelial cells in local pulmonary immune regulation. Medium conditioned by confluent monolayers of A549 cells suppressed proliferation by human peripheral blood mononuclear cells (PBMC) stimulated with lectin, anti-CD3 antibodies, calcium ionophore and phorbol ester, or in a mixed leukocyte reaction. PBMC that had been incubated in and then removed from A549-conditioned medium went on to proliferate normally. Because the suppressive effect was abrogated by heating or acidification and was not blocked by neutralizing antibody to transforming growth factor-beta 1, this effect could not be attributed to transforming growth factor-beta. The factor mediating this effect has an approximate molecular weight of 70,000 D by gel filtration chromatography. Nonalveolar, pulmonary carcinoma cell lines did not exert this immunosuppressive influence nor did the alveolar epithelial cells inhibit proliferation by the transformed, Jurkat, T-cell line. Cell cycle analysis demonstrated that PBMC exposed to A549 cell-conditioned medium failed to enter S phase after mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Factors↗
PubMed1992

Occurrence of antibodies to pneumococcal protein antigens in experimental acute otitis media.

To study serological antibody response to pneumococcal protein antigens, experimental pneumococcal (type 3) acute otitis media (AOM) was induced in 6 rats, sera being analysed with the Western blot technique at different intervals after bacterial challenge. The most striking finding was a distinct antibody response to a protein of about 35 kDa visible in 5 of the rat sera within 14 days, and persisting throughout the remainder of the study (i.e., 56 days in all). Moreover, appear to be a phenomenon restricted to type 3 pneumococci. Both the pathogenetic importance of this protein and the immunological response it evokes are still unclear. However, as antibodies to protein antigens may contribute to inflammatory reactions in the middle ear (e.g., otitis media with effusion), this 35-kDa protein might be important for the development of sequelae to AOM.

Acute Disease↗
PubMed1992

[Pachymeningeosis(-itis) haemorrhagica chronica interna].

A case of chronic internal haemorrhagic pachymeningeosis, a rare disease with uncharacteristic clinical appearance is presented. Derived from pathomorphological and histological findings, the typical CT appearance is described and main differential diagnoses are marked off by their characteristic criteria.

Dura Mater↗
PubMed1991

Western blot analysis of immunoglobulin G antibodies to pneumococcal protein antigens in healthy adults.

Using the Western Blot technique, sera from apparently healthy individuals were shown to contain antibodies against pneumococcal protein antigens of different molecular weights. A remarkable correlation was found to exist between the number of protein bands stained and the level of antibodies to type-specific carbohydrate antigens and C-polysaccharide. The findings suggest that the presence of antibodies against protein antigens reflects past infection with pneumococci.

Adult↗
PubMed1991

Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1 beta content but not monokine secretion in healthy and insulin-dependent diabetic individuals.

The effects of dietary supplementation with omega-3-polyunsaturated fatty acids (omega-3-PUFA) on the proliferative response of PBMC and on the secretion of monokines and arachidonic acid metabolites from PBMC and monocytes (Mo) from healthy subjects and patients with recent-onset insulin-dependent diabetes mellitus (IDDM) were examined. Three groups of eight to nine healthy individuals were randomized to either 2.0 g/day or 4.0 g/day of omega-3-PUFA devoid of vitamins A and D, or an isocaloric amount of placebo. Furthermore, eight patients with recent-onset IDDM received 4.0 g/day of omega-3-PUFA. IL-1 beta production and TNF-alpha secretion was determined before and after 7 weeks of treatment, and 10 weeks after withdrawal of treatment. Significant increases in platelet and PBMC membrane eicosapentaenoic acid was found in omega-3-PUFA-treated individuals. omega-3-PUFA treatment significantly reduced the content of IL-1 beta in lysates of PBMC, but did not affect PBMC or Mo secretion of IL-1 beta, TNF-alpha or prostaglandin E2 (PGE2) or PBMC leukotriene B4 (LTB4) secretion in healthy subjects or in IDDM patients. A significant inhibition of the PHA-stimulated, but not the spontaneous or PPD-stimulated, proliferative response of PBMC was observed in healthy and diabetic subjects treated with omega-3-PUFA. No correlation was found between PHA-stimulated PBMC proliferation and PBMC secretion of TNF-alpha and IL-1 beta. There were no significant differences in the spontaneous or the PPD- or PHA-stimulated proliferative responses of PBMC between diabetic and healthy individuals at entry. We conclude that although dietary supplementation with 4.0 g/day of omega-3-PUFA inhibits the proliferation of PBMC and reduces IL-1 beta immunoreactivity in PBMC and Mo, it does not alter monokine, PGE2 or LTB4, secretion in healthy or IDDM subjects.

Adult↗
PubMed1991

Measurement of transcutaneous PO2, PCO2 and skin blood flow at different probe temperatures using mass spectrometry.

Transcutaneously measured partial pressures of oxygen and carbon dioxide (PtcO2, PtcCO2) approximate the corresponding arterial values at a probe temperature of 44 degrees C. The temperature-dependent increase of PtcO2 and PtcCO2 is caused by an increased skin perfusion, a decrease in the mean diffusion path, a change of skin metabolism, a decrease of tissue solubility of oxygen and carbon dioxide and a right shift of the oxygen and carbon dioxide binding curves of blood. Seven healthy volunteer test subjects participated in the study. A transcutaneous probe connected to a mass spectrometer was placed on the earlobe of the test subject. Four measurements of the transcutaneous PO2, PCO2 and skin blood flow (from the washout kinetics of argon) were determined on each test subject. The first measurement was made with a transcutaneous probe temperature of 37 degrees C. The probe temperature was then increased to 44 degrees C before the next determination. Finally, two determinations were made at 37 degrees C, separated by a time interval of 1 h. The PtcO2 and skin blood flow increased when the probe temperature increased from 37 degrees C to 44 degrees C. However, when the probe temperature was decreased again from 44 degrees C to 37 degrees C, the estimated skin blood flow returned to the initial value while the PtcO2 remained unchanged. It required a further 1 h before the PtcO2 returned to the initial value at 37 degrees C. The most likely explanation of the experimental results is that heating of the skin to 44 degrees C causes a reversible decrease in the skin metabolism.

Adult↗
PubMed1991

Computer localization of some Gm markers on the surface of the Fc region of human immunoglobulin G.

The surface localization of some Gm markers on the Fc fragment of IgG has been identified from previously published amino acid sequences associated with known Gm markers using the atomic coordinates described by Deisenhofer, INSIGHT software and a Digital VAX 11/785 computer, which together permit a study of the three-dimensional structure of the Fc fragment. The G1m(x)-associated amino acid residue 431, the G3m(s)- and G3m(u)-associated residue 435 and the nG4m (a)- and (b)-associated residue 309 are all localized in the interface between the CH2 and CH3 domains. Furthermore, it is postulated that the G1m(a)-associated residue 356 (Asp, Glu) influences the interface formation through an ion pair interaction to Lys 439. Finally, G3m(b) and G3m(g) are associated with the interface via residues 435 and 436. The data explain why sera from patients with rheumatoid arthritis are useful tools for the detection of some Gm markers and support the view that rheumatoid factors from these patients are internal images of microbial Fc-binding proteins.

Computer Simulation↗
PubMed1991

Erythromycin and phenoxymethylpenicillin (penicillin V) in the treatment of respiratory tract infections as related to microbiological findings and serum C-reactive protein.

Respiratory tract pathogens (beta-haemolytic streptococci groups A, C and G, Haemophilus influenzae, Branhamella catarrhalis or pneumococci), were isolated from nasopharyngeal and/or throat swabs in 73/138 (53%) patients greater than 10 years of age with a clinical diagnosis of acute sinusitis, acute tonsillitis, purulent nasopharyngitis or acute bronchitis. Serological evidence of a viral infection (influenza A and B, parainfluenza 1, 2 and 3, respiratory syncytial virus, adenovirus) or Mycoplasma pneumoniae infection was found in 10% of the patients. The serum content of C-reactive protein (S-CRP) was increased (greater than 12 mg/l) in 26/33 (79%) patients with streptococci and in 22/59 (37%) patients without respiratory tract bacteria. In patients with a serological evidence of a virus tonsillitis, the S-CRP was also high (32-64 mg/l). At follow-up 10-12 days after the first visit, the clinical effect of erythromycin and penicillin V was judged to be similar (90% clinical effect). Relapse or re-infection with group A streptococci were seen in 7 patients (4 on erythromycin, 3 on penicillin). In another 6 patients (3 on erythromycin, 3 on penicillin), antibiotic treatment was switched owing to persisting symptoms, probably due to H. Influenzae infection in 3 cases. The patients' own estimates of their symptoms suggested treatment with erythromycin to have a more rapid effect than treatment with penicillin.

Acute Disease↗
PubMed1990

[Screening methods for microalbuminuria in diabetes mellitus].

Persistent microalbuminuria indicates early development of nephropathy, cardiovascular disease and death in patients with diabetes mellitus. In this study morning urines from 189 diabetic patients were investigated with conventional dip sticks, microbumintest and quantitative measurements obtained by immunturbidimetry. Microbumintest has both a higher specificity and sensitivity compared to urinary dip sticks. The immune chemical method is less expensive and alternations in albumin excretion rate can be followed. Quantitative measurement with an immunchemical method is therefore recommended as screening method for microalbuminuria.

Adolescent↗
PubMed1990

Functional and morphological effects of interleukin-1 beta on the perfused rat pancreas.

We recently reported a potentiating effect of recombinant human interleukin-1 beta on glucose-stimulated insulin release from the isolated perfused pancreas. With the aim of determining whether the stimulatory effect of recombinant interleukin-1 beta on the B cell in the intact gland was modulated by varying the concentration, time of exposure to recombinant interleukin-1 beta or B-cell activity, and to elucidate a possible mechanism of action, we measured in the perfused rat pancreas the release of insulin, glucagon and/or prostaglandin E2 according to the following three different protocols: (1) perfusion with 20 ng/ml of recombinant interleukin-1 beta for 92 min at 5 and 20 mmol/l D-glucose (2) perfusion with varying concentrations of recombinant interleukin-1 beta ranging from 0.1 x 10(-3) ng/ml to 100 ng/ml at 5 and 20 mmol/l D-glucose (3) perfusion with 20 ng/ml of recombinant interleukin-1 beta at 5, 11 or 20 mmol/l D-glucose. Furthermore, in a separate set of experiments we examined the influence of the cytokine on the morphology of the endocrine pancreas. Interleukin-1 beta stimulated insulin secretion at 11 and 20 mmol/l D-glucose and potentiated first as well as second phase insulin release in a dose-dependent fashion, with decreasing effect at higher concentrations. Glucagon secretion was also stimulated by recombinant interleukin-1 beta, irrespective of increasing glucose (5, 11, 20 mmol/l) and insulin concentrations. The potentiating effect of recombinant interleukin-1 beta on insulin secretion was evident even after discontinued perfusion with the cytokine, suggesting a priming effect on B-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Western blot analysis of the antibody response in patients with Listeria monocytogenes meningitis and septicemia.

The antibody response in patients with Listeria monocytogenes septicemia and/or meningitis was investigated using Western blot analysis (WBA). Protein antigen preparations were produced from two strains of Listeria monocytogenes, representing serogroup 1 and 4, by sonication and differential centrifugation. IgG antibodies from 8 (50%) of 16 patients with culture verified septicemia and/or meningitis due to Listeria monocytogenes reacted with a 93 kDa antigen from serogroup 1, in contrast to IgG antibodies from only 1 (2%) of 51 controls; these controls represented 21 patients with infections caused by other bacteria and 30 apparently healthy blood donors. Furthermore, IgM antibodies from 3 (19%) of the patients with listeric infections bound to a 106 kDa protein antigen in contrast to none of the controls. In 3 (33%) of 9 patients from whom acute and convalescence serum were available, the patients responded by producing antibodies against new protein antigens. Current methods used in routine serological investigations, i.e. complement fixation and O-agglutination tests, were positive in only 4 (24%) of the 16 patients with listeriosis. The results point to the possibility of designing new immunoassays for detection of septicemia and meningitis caused by Listeria monocytogenes.

Antibodies, Bacterial↗
PubMed1990

Possible role of microbial IgG Fc-binding proteins in rheumatoid arthritis.

IgG Fc binding substances (receptors) are widespread among pathogenic microorganisms. The receptors from Staphylococcus aureus, streptococci of group A, C and G as well as Herpes-infected cells bind to the interface between the CH2 and CH3 domains i.e. to His 435, Tyr 436 and possibly also His 433 and/or 310. Most rheumatoid factors (RF) from patients with rheumatoid arthritis show a similar binding pattern. Hence, it has been shown that antibodies to microbial IgG Fc receptors (S. aureus and group A streptococci type M15) and RF are idiotypic-anti-idiotypic antibody "partners" i.e. that RF are the "internal images" of microbial IgG Fc binding proteins. Group A streptococci possessing IgG Fc receptors elicit higher titres of RF when injected in rabbits as compared to group A streptococci without IgG Fc receptors. The streptococcal IgG Fc receptors exhibit a diversity of preferences for subclasses of human IgG, some of them showing allotype preferences. Such allotypes are also recognized by certain RF. IgG RF are able to self-associate thereby forming immune complexes which can activate the complement cascade as well as stimulate release of prostaglandins and (probably) interleukin-1. Since these factors have been assigned an important pathogenic role in rheumatoid arthritis, self-aggregating IgG RF, proposed to be induced by microbial IgG Fc receptors might be an important pathogenic factor in rheumatoid arthritis because rheumatoid arthritis is the only known condition where synthesis of RF takes place in the synovia.

Antigens, Differentiation↗
PubMed1990

Protective effect of heterologous gram-positive vaccine against lethal upper respiratory tract infection with type M50 group A streptococci in mice.

Type M50 group A streptococci are exceptional for their virulence in mice. However, intranasal (i.n.) vaccination with heat-killed group A streptococci, either of type M50 or M55, or an M12 strain deficient in M-protein, protected mice against i.n. challenge with M50 streptococci (82, 88 and 83% survival, respectively). Significant resistance against M50 streptococci was also noted by i.n. application of heat-killed Lactobacillus fermenti (81% survival) as well as two strains of pneumococci (50 and 79% survival). In contrast, no protective effect was obtained using heat-killed trypsin-treated M55 streptococci. Nor did vaccination with Escherichia coli and Pseudomonas aeruginosa induce protection against type M50. Thus, M protein was not required for immunity against type M50. The results call for a revision of the hitherto accepted view that M proteins are the only candidates for mucosal vaccines against group A streptococci.

Administration, Intranasal↗
PubMed1990

Gestational profile of the stimulatory effects of porcine amniotic and allantoic fluids on prostaglandin G/H synthase activity.

The effects of porcine fetal fluids (amniotic and allantoic) on microsomal prostaglandin G/H synthase (PGHS) activity were assessed. Both amniotic and allantoic fluids obtained from late-gestation sows stimulated PGHS activity (as indicated by increased formation of radiolabelled prostaglandin) in a dose-dependent manner. At the maximum dose tested, amniotic and allantoic fluids stimulated prostaglandin (PG) formation by 55.5 +/- 1.5 and 58.5 +/- 4.7%, respectively (n = 3, P less than 0.01). Based upon ED50 values, amniotic fluid was approximately threefold more effective than allantoic fluid in stimulating PG formation. The stimulatory effect of amniotic but not allantoic fluid increased significantly (P less than 0.01) during gestation (Days 47-112). The observed changes in the stimulatory effect of amniotic fluid on microsomal PG formation parallels the in vivo changes that occur in intra-uterine PG synthesis. Amniotic fluid stimulatory activity may contribute to this gestational increase in PG synthesis.

Allantois↗
PubMed1990

Monocyte function in IDDM patients and healthy individuals.

Interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) may be pathogenetically important in insulin-dependent diabetes mellitus (IDDM), which is associated with genes of the HLA region. Since a regulatory role of HLA region genes on monokine production may exist, we looked for an association between the monokine and prostaglandin E2 (PGE2) responses of monocytes (Mo) from 20 healthy males (18-50 years) with HLA-DR types relevant for IDDM susceptibility and resistance (DR1,2, DR1,3, DR1,4, DR3,4). Monokine assays were established and evaluated and the secretions of IL-1 beta, TNF-alpha, and PGE2 measured in Mo cultures (2h, 6h, 20h) prepared by endotoxin-free techniques and stimulated by low-dose E. coli lipopolysaccharides (LPS). There were no significant associations between Mo responses and HLA-DR phenotype. Likewise, Mo from DR2 (n = 5) and DR4 (n = 5) homozygous healthy males demonstrated no significant differences in monokine and PGE2 responses of Mo. In the HLA class III region a diallelic TNF-beta gene NcoI polymorphism consisting of alleles of 5.5 kb and 10.5 kb was recently described and associated with susceptibility to autoimmune diseases including IDDM. We report that IL-1 beta and TNF-alpha responses of Mo from TNF-beta 10.5 kb homozygous healthy individuals were significantly higher than for TNF-beta 5.5/10.5 kb heterozygotes. IL-1 beta and TNF-alpha responses of Mo from males (18-35 years) with newly diagnosed (n = 10) and long-standing IDDM (n = 10) and from age- and HLA-DR-matched healthy males (n = 10) were studied. LPS, gamma interferon (IFN), and TNF-alpha-stimulated Mo cultures were investigated. No significant differences were found between Mo responses of IDDM patients and controls. IFN (1000 U/ml) in the presence of LPS significantly potentiated LPS-stimulated Mo TNF-alpha secretion and reduced the levels of IL-1 beta immunoreactivity in Mo lysates. IFN and TNF-alpha did not have any effects on LPS-stimulated Mo secretion of IL-1 beta immunoreactivity. We conclude that Mo IL-1 beta and TNF-alpha production is normal in patients with recent-onset and long-standing IDDM. The interindividual differences in monokine responses may be accounted for by the diallelic human TNF-beta gene polymorphism rather than by HLA class II genes. This observation may be important for understanding the association of certain HLA haplotypes with autoimmune phenomena and disease.

Adolescent↗