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Biomedical subjects

P Christensen

Publications and source records attributed to P Christensen.

At least 109 records · Page 6Linked to original sources

Bartter's syndrome--treatment with potassium, spironolactone and ACE-inhibitor.

The treatment of Bartter's syndrome is fraught with difficulties, and there is no consensus concerning the pathogenetic mechanisms involved. Potassium depletion with hypokaliaemia is a dominant feature of the syndrome. In this case history, a 42-year-old woman suffering from Bartter's syndrome did not improve on several therapeutic trials. An impressive progress was noted, however, after intensive potassium repletion with subsequent potassium/spironolactone/ACE-inhibitor treatment. After 24 months her condition was unchanged with normal and stable Se-potassium concentration.

Adult↗

The Magill-Venturi attachment: studies in volunteers and patients.

Including a venturi injector in a Magill breathing attachment reduces the requirement of compressed gases to 40% of that normally used: 100-120 ml x kg-1 x min-1. The entrainment of ambient air through the venturi injector enables the supply of an adequate flow of gas mixture to the patient. In 10 awake volunteers and 12 patients under N2O/halothane anaesthesia, it was demonstrated that a fresh gas flow from the anesthetic machine of 40 ml x kg-1 x min-1 is sufficient to prevent rebreathing during spontaneous respiration, when the venturi injector is included in the Magill attachment.

Adult↗

Reduced rate of postoperative infections in emergency cesarean section after two doses of cefuroxim perioperatively. A placebo-controlled study.

The rate of postoperative infections after cesarean section was studied in a prospective double-blind randomized study to compare cefuroxim with a placebo. Intravenous bolus injections were given at the beginning of, and 12h after the operation. Eighty patients received cefuroxim and 80 received placebo. Endometritis or wound infection, or both, was diagnosed in 2/80 (2.5%) patients receiving cefuroxim and in 23/80 (29%) patients receiving placebo. No side effects were demonstrated or reported by the patients. Thus, two bolus injections of 1.5 g of cefuroxim given perioperatively significantly reduced postoperative infectious morbidity after emergency cesarean section.

Adolescent↗

Herpes simplex type 1-induced Fc receptor binds to the Cgamma2-Cgamma3 interface region of IgG in the area that binds staphylococcal protein A.

The binding site of immunoglobulin G (IgG) to herpes simplex virus (HSV) type 1-induced Fc receptor was investigated using human IgG Fc intermediate (Fc(i)) fragments, fragment D of staphylococcal protein A (SPA) and chemically modified human IgG. Human IgG Fc(i) fragment composed of one Cgamma2 and two Cgamma3 domains, bound strongly to HSV-1-infected cells. Fragment D, a monovalent subunit of SPA, inhibited the binding of radiolabelled human IgG Fc fragments to the HSV Fc receptor. Reductively methylated human IgG reacted equally well to HSV-infected cells, as did chemically unmodified IgG in contrast to N-acetylimidazole-modified and diethylpyrocarbonate-modifed human IgG, which were unreactive. These results suggest a similar binding site on human IgG for SPA and the HSV-1 Fc receptor with involvement of the amino acid residues Tyr and His but not Lys. The similarities of binding sites on the IgG molecule for the HSV-1 Fc receptor and rheumatoid factors (RF) may be important for understanding the mechanism of RF production in rheumatoid arthritis or other disease states.

Animals↗

Nonlinear curve fitting improves noise sensitivity of the single-breath method for estimation of cardiac output.

In a recent theoretical study, Srinivasan (10) presented a new nonlinear curve fitting algorithm for computing pulmonary blood flow by the single-breath method. The results obtained with the new algorithm showed a considerably lower sensitivity of the estimated pulmonary blood flow to experimental noise than with the linear curve fitting technique reported previously by Grønlund (5). In the present study, we have compared the linear and the nonlinear algorithms using computer simulations and experimental single-breath data. The results showed only a small difference between the two methods. Further, we showed that the difference between the noise sensitivities obtained by Grønlund (5) and Srinivasan (10) can be explained almost entirely by a difference between the models used to simulate experimental noise.

Algorithms↗

Gestational profile of prostaglandin E2 synthesis by porcine placenta and fetal membranes.

The capacity of the diffuse, epitheliochorial porcine placenta (chorioamnion plus endometrium: AMCE and chorioallantois plus endometrium: ALCE) and allantoamnion (ATA), obtained from sows at 47-112 days of gestation (n = 12), to release PGE2, during in vitro explant incubation, was determined. There was no significant difference between PGE2 release from AMCE and ALCE, and the data obtained from these two tissues were pooled. The release of PGE2 from ATA was, at all stages of gestation, significantly less (8-50 fold; p less than 0.01, n = 12) than that released from AMCE/ALCE. During gestation, the basal release of PGE2 from AMCE/ALCE increased from 13.7 +/- 2.8 pmol/100 mg per incubation (n = 8; mean +/- S.E.M.) at less than 80 days to a maximum of 176.5 +/- 30.9 pmol PGE2/100mg per incubation (n = 10) at greater than 109 days of gestation. Basal PGE2 release from ATA increased from 1.6 +/- 0.6 pmol PGE2/100 mg per incubation (n = 3) at less than 80 days to 3.5 +/- 0.5 pmol PGE2/100 mg per incubation at greater than 109 days gestation. At all stages of gestation and in all tissues, the addition of sodium arachidonate significantly stimulated PGE2 release, indicating that during gestation prostaglandin synthesis by porcine placenta and fetal membranes is, at least partly, substrate limited. The observed increase in the release of prostaglandin E2 from placenta and fetal membranes that occurred from 90 days of gestation and rapidly increased at term may reflect an increase in substrate availability, an increase in the activity of prostaglandin endoperoxide H synthase- E isomerase or a combination of these processes.

Animals↗

Endoscopic suspension of the bladder neck by the Stamey method for urinary incontinence.

Eighteen women with stress incontinence underwent endoscopic suspension of the bladder neck by the method of Stamey. The procedure was carried out in a department of general surgery. Pre- and postoperatively the patients were evaluated by pelvic examination with stress test, colpo-cysto-urethrography, urinary flow rate measurement, cystometry, and culture of the urine. Fifteen became fully continent at once, another two after having been treated further by posterior colpoperineorraphy, while one remained incontinent. The median postoperative follow-up was 27 months. Complications were rare and mild. It is concluded that the method is applicable in departments of general surgery and that the result can be improved in selected patients by posterior colpoperineorraphy.

Adult↗

Urinary prostaglandin E2 and F2 alpha excretion in nephrotic syndrome during basal conditions, after water loading, and after remission of the syndrome.

The urinary excretion rate of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) was determined in patients with the nephrotic syndrome both before and after an oral water load in 21 patients and 17 control subjects, and before and after remission of the syndrome in 8 of the patients. In the nephrotic syndrome PGE2 excretion rate varied considerably during basal conditions, remission was accompanied by an increase in the PGE2 excretion, and both basal PGF2 alpha excretion rate and the normal response in PGF2 alpha water loading were reduced. A significant, positive correlation was found between urine flow rate and excretion rate of PGE2 in the periods with the largest urine flow rate in both patients and control subjects. It is suggested that a relatively suppressed renal prostaglandin production may be a pathogenetic factor for sodium and water retention in the nephrotic syndrome, although it cannot be excluded that the abnormal prostaglandin excretion pattern is secondary, at least partially, to the reduction of urine flow rate.

Adult↗

Disturbed relationship between urinary prostaglandin E2 excretion, plasma arginine vasopressin and renal water excretion after oral water loading in early hepatic cirrhosis.

An oral water load of 20 ml kg-1 body weight was given to 11 patients with early hepatic cirrhosis and to 16 healthy control subjects. Urinary output (V), free water clearance (CH2O), urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), and plasma concentration of arginine vasopressin (AVP) were determined before and during the first 4 h after loading. During basal conditions, PGE2 excretion was the same in patients (75 pg min-1, median, range 15-569) and controls (78 pg min-1, range 22-262), but during the first hour after water loading, PGE2 increased to a significantly higher level in cirrhotic patients (423 pg min-1, median) than in control subjects (162 pg min-1) (P less than 0.05). No difference in PGF2 alpha excretion was found between the two groups. Urinary output and CH2O were significantly lower after water loading in patients than in controls. Arginine vasopressin before water loading did not differ between patients and control subjects, but after loading it was unchanged in the patients, whereas a significant reduction (1.9 to 1.4 pmol l-1, P less than 0.01) was found in the control subjects. In controls, but not in patients, PGE2 was significantly positively correlated to V and CH2O, and negatively correlated to AVP after water loading. Thus, renal PGE2 excretion is increased and CH2O is decreased after water loading in patients with early hepatic cirrhosis, and a disturbed relationship seems to exist between PGE2 on the one hand, and AVP and renal water excretion, on the other, in these patients after water loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences.

The secretions of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPS)-stimulated human monocytes (M phi) were investigated in an endotoxin (ET)-free milieu (less than 1.6 pg LPS/ml). Human M phi cultures from nine healthy men were stimulated with 0, 12.5-500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22-24%, intra-assay variation 3-7%). Spontaneous M phi secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these M phi products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR1,2-positive, were identified. Three first-degree relatives of the DR1,2-positive low-responder had similar low responses. Furthermore, M phi cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2,2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated M phi were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.

Biological Products↗

Afternoon plasma cortisol in relation to depression. A replication study.

In 37 consecutive depressed inpatients afternoon plasma cortisol (1500-1520 h) was measured in 3 ways: 1) spontaneously; 2) 2 h after oral administration of 60 mg oxazepam; and 3) 16 h after oral administration of 2 mg dexamethasone. Both oxazepam and dexamethasone caused a significant suppression of cortisol secretion. Spontaneous and suppressed cortisol levels correlated significantly to stress/distress items on the Hamilton Rating Scale for Depression (sum of items 8, 9, 10 and 12), whereas no correlations to age, or type of depression were found. In an earlier similar study of 35 patients both spontaneous and suppressed cortisol levels correlated significantly with age, type and severity of depression as well as with the stress/distress items. Those patients were older, more depressed (HRSD-17) and had higher stress/distress scores compared with the present sample of 37 patients. The consistent finding of a correlation with the stress/distress items suggest that this factor is important in relation to the hypersecretion of cortisol during depression and this may explain the limited diagnostic power of spontaneous and suppressed cortisol levels.

Adult↗

Molecular interactions between human IgG, IgM rheumatoid factor and streptococcal IgG Fc receptors.

Group A streptococci type M15 were previously shown to bind both human IgG via the Fc component and a purified monoclonal IgM kappa rheumatoid factor (IgM RF). Using 125I-labelled IgG and 125I-labelled IgM RF, the present study gave association constants of 2.2 x 10(7) and 2.9 x 10(8) M-1, respectively. The binding of 125I-IgG to the streptococci was inhibited by unlabelled IgG, IgG Fc and fragment D of staphylococcal protein A but not by the IgM RF or F(ab')2 of anti-idiotype antibodies to RF (anti-Id RF). Inversely, unlabelled IgM RF and anti-Id RF inhibited the binding of 125I-IgM RF markedly and unlabelled human IgG and IgG Fc only slightly or moderately, respectively. Thus, group A streptococci type M15 showed different binding sites for IgG Fc and the antibody combining sites of a human monoclonal RF. The findings were still more complex on a background of previous reports showing that streptococcal IgG Fc receptors and RFs bind to the same amino acids on the Fc molecule. This complex pattern may play a role in the pathogenesis of rheumatoid arthritis.

Binding Sites, Antibody↗

Neonatal septicemia due to group B streptococci--perinatal risk factors and outcome of subsequent pregnancies.

All cases of early onset group B streptococcal (GBS) septicemia in infants born at Karolinska Hospital 1975-1986 were reviewed. GBS-septicemia was diagnosed in 40 infants within the first five days of life. The incidence was 1.24 per 1000 births. Fifty-five percent of the infants were preterm and 48% were born more than or equal to 12 hours after rupture of membranes. Prematurity and/or prolonged rupture of membranes were present in 83% of all neonates with fatal outcome. Case fatality was 22%. Deliveries by both cesarean section (31%) and vacuum extraction (26%) were increased in the mothers when compared to an overall incidence of 14 and 12% (p less than 0.01). Twenty-four (89%) of 27 mothers had low type specific IgG antibodies against the infecting GBS-serotype. Late onset GBS-septicemia was diagnosed in only two infants during the period. Seventeen mothers went through 24 subsequent pregnancies. In 11 of those the mothers were colonized with GBS and 10 received penicillin prophylaxis during pregnancy and/or delivery. None of the infants born after prophylaxis were colonized with GBS. Two were born prematurely and all had an uneventful course; whereas one infant delivered at 26 weeks gestation of a colonized untreated mother died of GBS-septicemia. Screening of parturients at risk and selective antibiotic prophylaxis may help to prevent early onset GBS-septicemia.

Antibodies, Bacterial↗

Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to the Fc binding proteins of microorganisms.

Work from our laboratories has shown that the major antigenic determinants for rheumatoid factors (RFs) are in the C gamma 2-C gamma 3 interface region of IgG in the same area that binds staphylococcal protein A (SPA). Furthermore, the Fc binding proteins of groups A, C and G streptococci as well as the Fc binding proteins induced on cell surfaces by herpes simplex virus type I also bind to the same area of IgG. These binding site similarities between RFs and the microbial Fc binding proteins suggested conformational similarities between the RF antigen combining regions and the Fc binding regions of the microbial proteins. This hypothesis was supported by the observation that antibodies to SPA bind to the antigen combining regions of most RFs as well as to the Fc binding region of the T15 group A streptococcal Fc binding protein. These findings indicate that RFs bear the conformational internal image of these microbial proteins and suggest that RFs could arise as antibodies to the idiotypic determinants on antibodies to microbial Fc binding proteins. Alternatively, microbial Fc binding proteins could present IgG to the immune system in a way that renders specific areas of the C gamma 2-C gamma 3 interface region immunogenic. These relationships between RFs and microbial Fc binding proteins may prove to be important for our understanding of the generation of RFs in rheumatoid arthritis.

Binding Sites↗

Molecular mimicries between human IgG, IgM rheumatoid factor and streptococcal IgG Fc receptors.

A monoclonal IgM rheumatoid factor (RF) from a patient with mixed essential cryoglobulinaemia was found to bind to type M15 group A streptococci with high affinity. The reaction was exerted via the antibody combining sites since it was inhibited by F(ab')2 fragments of anti-idiotypic (Id) antibodies but not by F(ab')2 of anti-IgMFc or normal rabbit IgG. The streptococcal strain also possessed receptors for the Fc part of IgG. IgMRF and IgG attached to different sites on the streptococcal surface, since e.g. anti-Id did not inhibit the IgG Fc-receptor binding. Furthermore, it was found that the interaction between the streptococcal IgG Fc receptor and IgG--like the RF/IgG interaction--took place in the interface between C gamma 2 and C gamma 3 and that histidine 435, tyrosine 436 and/or one both of histidine 433 and 310 were involved.

Animals↗