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Biomedical subjects

P Christensen

Publications and source records attributed to P Christensen.

At least 91 records · Page 5Linked to original sources

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

Repeatability of the acetylene rebreathing method in measuring cardiac output: influence of acetylene concentration.

The acetylene rebreathing method is a reliable noninvasive method for estimation of cardiac output. However, the method is not commonly used for clinical purposes. This is due mainly to the fact that acetylene is explosive at concentrations above 2% and that acetylene at concentrations above 0.5% has an unpleasant taste. In the present study we have investigated whether it is possible to reduce the concentration of acetylene to 0.3% in the rebreathing bag without degrading the repeatability of the estimated cardiac output. The problem was elucidated theoretically and experimentally. A theoretical investigation was carried out by producing an acetylene rebreathing curve from a single alveolus lung model. The theoretical study showed that the random noise arising from the gas analyzer gives rise to less than 10% of the total variation of the estimated cardiac output. The results of the experimental study showed that it is possible to reduce the acetylene concentration to 0.3% without decreasing the reproducibility of the acetylene rebreathing method.

Acetylene↗

Duodenal disappearance rate of acid during inhibition of mucosal bicarbonate secretion.

In order to investigate the relation between duodenal mucosal and pancreaticobiliary bicarbonate secretion, we have studied the effect of inhibition of mucosal bicarbonate secretion by indomethacin on the disappearance rate of acid and the concomitant plasma secretin concentrations. 10 healthy subjects were studied twice, with and without indomethacin pretreatment. By means of a double-lumen tube the duodenum was perfused with increasing amounts of acid (0, 3.0, 6.0 and 9.5 mmol/h) and the disappearance rate of acid, pH of duodenal aspirate and plasma secretin were measured. In both experiments nearly all acid, even at the highest acid load, disappeared (pH greater than 6). Inhibition of the duodenal mucosal bicarbonate secretion did not decrease the acid-neutralizing capacity of the human duodenum. In fact, the disappearance rate of acid at the highest acid load was a little greater when mucosal bicarbonate secretion had been inhibited than when not (10.3 +/- 0.5 vs. 9.2 +/- 0.2 mmol/h). The pancreaticobiliary secretion of bicarbonate, as judged by plasma secretin concentrations, increased, however, earlier when mucosal bicarbonate secretion had been inhibited than when not (3.7 vs. 3.0 pmol/l at an acid load of 6.0 mmol/h). This indicates that bicarbonate from the duodenal mucosa normally plays a role in the in lumen neutralization of acid in the human duodenum.

Adult↗

Lack of transmission of HIV to sexual and non-sexual contacts to HIV seropositive haemophiliacs following preventive information.

In order to evaluate the risk of HIV transmission to sexual and non-sexual contacts to seropositive haemophiliacs, HIV antibodies, p24 antigen, immunoglobulin levels and lymphocyte subsets were analyzed in a cohort of Swedish haemophiliac families to 19 patients who seroconverted in 1980-82. As controls served contacts to 26 seronegative haemophiliacs. A total of 77 contacts were investigated. Except for 3 sexual partners who had seroconverted before 1985 no signs of HIV infection were detected. It was concluded that no HIV transmission occurred to household contacts of seropositive haemophiliacs and that transmission to heterosexual partners not appeared since 1985 when the patients and their families were informed about the risk of infection.

Adolescent↗

Captopril treatment in Bartter's syndrome.

A 13-year-old girl presented with lassitude, polyuria and hypokalemia. Plasma renin concentration and urinary prostaglandin excretion were elevated, whereas plasma aldosterone concentration, urinary aldosterone excretion and blood pressure were normal. A diagnosis of Bartter's syndrome was made. The result of treatment with oral potassium was unsatisfactory. Treatment with acetylsalicylic acid had some effect, but an allergic reaction rendered withdrawal necessary. Treatment with the angiotensin converting enzyme inhibitor captopril and oral potassium led to clinical and biochemical improvement.

Adolescent↗

Cortisol and treatment of depression: predictive value of spontaneous and suppressed cortisol levels and course of spontaneous plasma cortisol.

In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n = 72), 2) 2h after oxazepam suppression (45 mg, n = 28; 60 mg, n = 37) and 3) 16 h after dexamethasone suppression (2 mg, n = 71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n = 55) and 5 weeks' treatment (n = 36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.

Adult↗

Age-related variations in anti-streptococcal antibody levels.

The present study was undertaken to determine the upper 95% confidence limits (CL) for titres of antibodies to streptolysin O (ASO) and streptococcal DNase B (ADNB) using 741 sera from a general population. The ASO titres in sera from children increased abruptly with increasing age, from a mean of 21 (CL 67) in infants of 3 years or less to 211 (CL 462) in children 7 to 8 years old. In children 9 to 12 years of age titres exhibited a plateau with mean values of 168-258 (CL 436-611). In individuals over 20 years the mean ASO titre diminished with increasing age, individuals of 70 years or more showing a mean titre of 83 (CL 169). A similar variation was seen for ADNB. Infants 3 years of age or younger exhibited no detectable ADNB whereas individuals 70 years or more had a mean titre of 11 (CL 91). A maximal mean ADNB titre of 184 (CL 706) was detected in 9-year-old-children. It was concluded that age-related reference values for anti-streptococcal antibodies increase the clinical relevance of the tests.

Adolescent↗

Chlorhexidine for prevention of neonatal colonization with group B streptococci. V. Chlorhexidine concentrations in blood following vaginal washing during delivery.

Chlorhexidine 2 g/l was applied to the vagina of 96 women during delivery, whereas 28 served as controls. Both groups were given a shower using a chlorhexidine soap, and outer washing of the outer anogenital tract was also performed in all patients using chlorhexidine 2 g/l. Using a gas chromatographic method with a detection limit of 10 ng chlorhexidine per ml blood, 10-83 ng/ml was demonstrated in 34 (35%) of the study group patients, whereas the remaining study group patients and controls showed no detectable chlorhexidine. Performing the washing a second time after 6 hours in 14 patients and a third time in 3 patients after a further 6 hours did not result in increased serum levels. It was concluded that small amounts of chlorhexidine are absorbed through the vaginal mucosa and that chlorhexidine is not accumulated in the blood on repeated usage with 6 hour intervals during delivery.

Administration, Intravaginal↗

A biphasic response of urinary prostaglandin E2 excretion to water deprivation in conscious diabetes insipidus Brattleboro rats.

UNLABELLED: The effects of water deprivation on the urinary excretion rate of prostaglandin E2 (PGE2) were examined in conscious Brattleboro rats. In order to study the time course of the changes in the PGE2 excretory rate, urine was collected in 6 periods, CONTROL: 0-1 hour (h.). 1: 3-4.5 h., 8-10 h., III: 12-15 h., IV: 24-28 h. and V: 32-36 h. after removal of water and food. It was found that the PGE2 excretion rate changed in a biphasic pattern. During the first 2 experimental periods it increased. Thereafter it decreased towards the control value. There was an increase in PGE2 excretion with urinary flows down to 3 microliter/(min*100 g b. wt). At further reductions in urinary flow rate, PG excretion decreased towards basal levels.

Animals↗

Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients: significance of concurrent medication and the sparteine oxidation phenotype.

Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steady-state levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (rs = 0.68, n = 55, p less than 0.001) and the nortriptyline/Z-10-OH-nortriptyline ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p less than 0.01) and E-10-OH-nortriptyline (rs = -0.52, p less than 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

Adult↗