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Biomedical subjects

K Bergh

Publications and source records attributed to K Bergh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of anti-C5a antibody on blood-lung and blood-brain barrier in rabbits after decompression.

The complement activation product C5a may be an important mediator of tissue injury after decompression stress. This study investigated whether the administration of anti-C5a antibody may reduce changes after decompression in the lung and in the brain. Two groups of rabbits were used; one receiving anti-C5a monoclonal antibody (n = 7) and the other receiving a sham antibody as control (n = 7) before pressure exposure. Five rabbits (4 in the anti-C5a group and 1 in the control group) died during the 2-h observation period postdive due to massive bubbling. Polymorphonuclear leukocyte (PMN) infiltration of lung tissue and pulmonary edema was observed, but this accumulation was unaffected by anti-C5a pretreatment. However, a significant positive correlation was observed between PMN accumulation and survival time postdive. Brain-specific gravity was lower for the group treated with anti-C5a antibody compared to the control group. Further, it was lower for those rabbits that died early compared to the ones that survived the 2-h period. This study was unable to prove a protective effect on the blood-brain and blood-lung barrier by injecting anti-C5a antibody. A possible beneficial effect of anti-C5a antibody may be masked by the mechanical damage caused by the gas bubbles.

Animals↗
PubMed1998

[Spotted fever after travel to South Africa].

Three patients developed fever, malaise and a typical maculopapular rash a few days after returning to Norway from South Africa. In South Africa they had been bitten by ticks several times while hunting. Two patients, with lesions compatible with eschar, were hospitalized, and a diagnosis of rickettsial spotted fever was established based on the clinical presentation and positive Rickettsia conorii serology. Rickettsial diseases are extremely rare in Scandinavia, and a survey on rickettsioses is presented in this paper.

Boutonneuse Fever↗
PubMed1998

Effect of filtration and storage of platelet concentrates on the production of the chemotaxins C5a, interleukin 8, tumor necrosis factor alpha, and leukotriene B4.

BACKGROUND: The production in platelet concentrates (PCs) of C3 activation products (C3bc), terminal complement complex (TCC), and chemotaxins C5a, interleukin (IL)-8, tumor necrosis factor alpha (TNFalpha), and leukotriene B4 (LTB4) and the proposed reduction in concentration of the chemotaxins by white cell reduction were examined. STUDY DESIGN AND METHODS: Samples were collected from supernatants of PCs produced by apheresis (apheresis PCs) or from buffy coats (BC PCs) immediately after the production, after white cell-reduction filtration on Day 1, and after 5-day storage, and examined by enzyme immunoassays. RESULTS: Complement was activated in all PCs during storage, and the concentration of activation products was not influenced by prestorage filtration. In prestorage white cell-reduced BC PCs, only C3bc levels increased. Levels of IL-8, TNFalpha, and LTB4 increased during storage of apheresis PCs, but not in filtered units, except for LTB4. In contrast, levels of IL-8 decreased after storage of filtered BC PCs. C5a correlated significantly with IL-8, which also correlated with TNFalpha and LTB4. CONCLUSION: Both C5a and TNFalpha generation in apheresis PCs seem to induce white cell IL-8 production, which mediates cellular LTB4 release. Prestorage white cell reduction is recommended for reducing chemotactic cytokine and leukotriene levels in all PCs. Production of BC PCs is recommended to achieve less complement activation, which is not affected by filtration.

Blood Platelets↗
PubMed1998

Identification of nasopharyngeal carriage of an outbreak strain of Neisseria meningitidis by pulsed-field gel electrophoresis versus phenotypic methods.

The clustering of four cases of meningococcal disease during a 3-month period in a small community with 2233 inhabitants prompted an interventional carrier survey in persons < 19 years old and in family members of the patients. The aims of the survey were to identify the nasopharyngeal carriers and the carriage rate of the outbreak strain, to offer chemoprophylaxis to those carrying the outbreak strain, and to study the discriminatory power of phenotypic methods versus pulsed-field gel electrophoresis (PFGE) on carrier isolates during an outbreak. A high percentage of the population in the age group 0-19 years (73.7%) participated in the study. Among the 469 samples collected in this age group, meningococci were grown from 43 (9.2%). The highest carriage rates were in the age group 18-19 years (36.4%). With a provisional definition of the outbreak strain (group B or non-groupable Neisseria meningitidis with reduced sulphonamide sensitivity), six carriers were identified. All were treated with a single dose of ofloxacin. Four of these persons (0.76% of all tested) were later shown to have harboured the outbreak strain when analysed by PFGE. Three of them were epidemiologically closely related to one of the index cases. Serogrouping alone is not sufficient for the identification of an epidemic strain of N. meningitidis. Complete concordance of type and subtype antigens correctly identified the outbreak strain in this study. PFGE is well suited for the identification of an outbreak strain of N. meningitidis versus non-epidemic strains in tonsillo-pharyngeal specimens.

Adolescent↗
PubMed1998

Effects of cascade apheresis in patients with psoriasis and psoriatic arthropathy.

Eight patients with psoriasis, all with skin scales and 7 with disabling psoriatic arthritis, were subjected to cascade apheresis starting with three treatments per week for 2 weeks, followed by one treatment a week, comprising ten treatments in all. Six out of 7 patients (86%) with arthropathy and 3 out of 8 patients (38%) with scales experienced a beneficial effect. There was a large drop in the levels of circulating immune complexes (CIC) due to the treatment, and the removal of CIC was followed by reduced inflammatory activity in skin lesions and joints as evaluated by pain, morning stiffness, grip strength, plaque score, and PASI index. However, there was no correlation between the level of CIC, disease activity, or treatment response. From the present results it is concluded that CIC may play a more significant role regarding psoriatic arthropathy than in skin manifestations, and apheresis may be beneficial in patients not responding to conventional therapy.

Adult↗
PubMed1998

The pharmacokinetics of a new antiglaucoma drug, latanoprost, in the rabbit.

Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha-1-isopropyl ester) is a unique prostaglandin analogue developed for the treatment of glaucoma. To investigate the pharmacokinetics, tritium-labeled latanoprost was administered topically on the eyes of rabbits and intravenously. About 7.7% of the applied dose was found in the cornea at 15 min after the drug administration. The following Cmax and elimination half-life (interval 1-6 hr) values of the total radioactivity in the eye tissues were found: aqueous humor, 0.09 ng eq/ml and 3.0 hr; anterior sclera, 1.49 ng eq/mg and 1.8 hr; cornea, 1.59 ng eq/mg and 1.8 hr; ciliary body, 0.39 ng eq/mg and 2.8 hr; conjunctiva, 1.41 ng eq/mg and 1.4 hr; and iris, 0.39 ng eq/mg and 2.1 hr. Latanoprost was rapidly hydrolyzed, and most of the radioactivity found in the aqueous humor, anterior eye tissues, and plasma corresponded to the pharmacologically active acid of latanoprost. The initial plasma elimination half-life of the acid of latanoprost was 9.2 +/- 3.2 min after iv and 2.3 +/- 1.9 min after topical administration on the eyes. The plasma clearance of the acid of latanoprost was 1.8 +/- 0.3 liters/hr.kg, and the volume of distribution was 0.4 +/- 0.1 liter/kg after iv administration. Based on the retention times on HPLC and GC-MS, the main metabolite in urine and feces was identified as the 1,2,3,4-tetranor metabolite of acid of latanoprost. This acid existed in equilibration with the corresponding delta-lactone. The AUC of radioactivity in the eye tissues was approximately 1000 times higher than in plasma AUC. The recovery of radioactivity was complete.

Absorption↗
PubMed1997

Both plasma- and leukocyte-associated C5a are essential for assessment of C5a generation in vivo.

BACKGROUND: Measurement of C5a in plasma is hampered by the rapid clearance of C5a as a result of cell binding. Therefore, an assessment of whether cell-bound C5a might better reflect C5a generation in vivo is essential. METHODS: We quantified plasma and leukocyte-bound C5a in samples from patients undergoing cardiopulmonary bypass, which is known to be associated with complement activation. C3 activation products and the terminal complement complex were measured as well. RESULTS: Plasma levels of C3 activation products and the terminal complement complex increased rapidly and significantly after the onset of cardiopulmonary bypass until they reached a plateau after 30 minutes. The concentration of plasma C5a increased steadily to twice baseline at the end of bypass. The concentration of leukocyte-associated C5a increased threefold after 10 minutes of cardiopulmonary bypass, when a plateau was reached. A positive correlation was found between levels of plasma C3 activation products or terminal complement complex and plasma C5a plus cell-associated C5a but not between C3 activation products or terminal complement complex and either one of the C5a variables. CONCLUSIONS: We conclude that both plasma C5a and leukocyte-associated C5a are needed for monitoring in vivo C5a generation.

Cardiopulmonary Bypass↗
PubMed1996

TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense.

TNF mediates multiple biologic activities through two distinct cell surface receptors, TNFR-p55 and TNFR-p75. TNF plays an important role in nonspecific resistance against the fungus Candida albicans. We used transgenic mice deficient for TNFR-p55 or TNFR-p75 to investigate the role of the TNFR in antifungal defense. Mice deficient for TNFR-p55 have highly impaired ability to clear infection with C. albicans and readily succumb to the infection. Also mice deficient for TNFR-p75 had a significant reduction in their ability to clear the fungus although lethality was not increased. These data demonstrate that TNFR-p55 in particular, but also TNFR-p75, plays a definite role in defense against infection with C. albicans. In NMRI mice, infection with C. albicans resulted in a significant systemic release of soluble (s)TNFR-p75. Cyclophosphamide-induced granulocytopenia led to a reduction of sTNFR-p75 release, whereas levels of bioactive TNF in response to fungal infection were increased. Release of sTNFR-p55 was not affected by induction of granulocytopenia. These observations suggest that granulocytes are a source of sTNFR-p75, possibly contributing to regulation of TNF activity during infection with C. albicans.

Animals↗
PubMed1995

Complement activation in divers after repeated air/heliox dives and its possible relevance to DCS.

Plasma levels of the anaphylatoxin C5a were measured in 19 divers performing repeated air dives. Blood samples were collected immediately before the first dive and 2 h after the first and the second or third dive. Serum obtained at the same times was subjected to complement activation in vitro by air bubbles. Six divers developed symptoms of decompression sickness (DCS). Most intravascular bubbles were observed in divers with the lowest plasma levels of C5a. Postdive plasma levels of C5a did not increase compared with predive levels, nor were postdive levels significantly different after two or three dives compared with the first dive. Repeated dives did not influence the amounts of C5a generated in vitro. Neither plasma levels of C5a nor C5a generated in vitro were significantly different in divers who experienced symptoms of DCS vs. divers without symptoms of DCS. We conclude that plasma level of C5a and measurement of C5a generation in vitro cannot be used to predict DCS.

Adult↗
PubMed1994

Heparin-coated circuit during cardiopulmonary bypass. A clinical study using closed circuit, centrifugal pump and reduced heparinization.

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint-attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin-coated equipment (CBAS) and reduced i.v. heparin (1.5 mg.kg-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg.kg-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ng.ml-1 +/- 1.2 to 27.5 ng.ml-1 +/- 4.8 on day 2 and in the CBAS group from 10.7 ng.ml-1 +/- 1.2 to 35.6 ng.ml-1 +/- 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Activation of the complement system and adverse effects of biodegradable pins of polylactic acid (Biofix) in osteochondritis dissecans.

Biodegradable pins of polyglycolic acid (PGA) or polylactic acid (PLA) have been used in the treatment of fractures and osteotomies during the past 5 years. Adverse effects reported have included swelling at the implantation site and sinus formation, considered to represent nonspecific foreign-body reactions. Recent reports, however, have shown severe reactions after intraarticular fracture fixation. Reactions in 2 patients, treated with polylactic pins for osteochondritis dissecans (OCD) in our hospital, prompted the present clinical investigation and further evaluation of the complement-activating potential of polylactic pins. 10 knees underwent arthroscopic fixation of an OCD-lesion with Biofix (PLA) pins. Clinical follow-ups were carried out at 2, 6, and 12 weeks and at 6 and 12 months. Blood samples were collected from 5 patients 9-24 months postoperatively for biocompatibility tests. Quantification of human C5a des Arg was performed with a recently developed sandwich ELISA technique, using neoepitope-specific monoclonal antibodies. 6 knees developed diffuse swelling and a prolonged postoperative course. 2 patients had a particularly prolonged course which could not be attributed to infection. Levels of C5a des Arg in plasma incubated in the presence of polylactic acid were higher than in plasma incubated in the absence of PLA. The high frequency of long-term postoperative inflammatory signs in these knees treated for OCD and the demonstration of a complement activation potential of PLA pins warrant further studies on the biocompatibility of this material. Until more information is available, we do not recommend intraarticular use of PLA pins.

Adolescent↗
PubMed1993

[Severe gastroenteritis after domestic infection with Vibrio cholerae non-O1].

Vibrio cholerae non-O1 has previously been isolated only occasionally in Norway from patients infected abroad. This report describes the clinical course in two patients who were domestically infected with V. cholerae non-O1. In one case, contaminated seafood, i.e. crab, was the probable source of infection. Both patients displayed a cholera-like type of illness, with severe diarrhoea and electrolyte disturbances. It is recommended that Norwegian laboratories be prepared to isolate vibrios also in domestically infected cases when watery diarrhoea is present.

Aged↗
PubMed1993

Surprisingly high levels of anaphylatoxin C5a des Arg are extractable from psoriatic scales.

Water-soluble extracts from psoriatic scales and normal human skin were prepared using either phosphate-buffered saline, pH 7.2, or 0.1 M carbonate buffer, pH 10.8. Anaphylatoxin C5a des Arg was quantified using a novel sandwich enzyme-linked immunosorbent assay (ELISA) using neoepitope-specific monoclonal antibodies. Alkali was about five to eight times more efficient than PBS in extracting C5a des Arg from scales, probably via dissociation of bound C5a des Arg. C5a des Arg concentration in scales from three patients suffering from psoriasis vulgaris varied between 2.5 and 4.6 ng/mg scale. No C5a des Arg was detectable in normal skin extracts. The biological activity of alkali-extractable C5a des Arg, i.e. chemotaxis, was preserved. The concentration of C5a des Arg relative to the concentration of albumin was taken as a parameter of the degree of complement activation in the psoriatic lesions, and was found to be more than six times higher than values attained in serum after maximum complement activation by zymosan. We conclude that complement activation may play a quantitatively important role in the inflammatory process in psoriasis.

Antibodies, Monoclonal↗
PubMed1993

Effects of stem cell factor and granulocyte colony-stimulating factor on granulocyte recovery and Candida albicans infection in granulocytopenic mice.

The combined action of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on granulocyte recovery and infection with Candida albicans was studied. In mice rendered granulocytopenic with 200 mg/kg cyclophosphamide, daily coinjection of SCF (100 micrograms/kg) and G-CSF (10 micrograms/kg) for 5 days synergistically stimulated granulocyte recovery compared with either factor alone. Growth of C. albicans in the kidneys of granulocytopenic mice with experimental C. albicans infection was reduced by the combined regimen to 25% of that in vehicle-treated controls (P = .018), whereas either factor administered alone in the same doses had no effect. The combined regimen also significantly protected against lethal infection with C. albicans (P < .01). Either factor administered alone in the same doses had no effect on lethality compared with vehicle-treated controls. The combination of SCF and G-CSF may be useful in the treatment of infections with C. albicans in the granulocytopenic host.

Agranulocytosis↗
PubMed1993

Variability over time of complement activation induced by air bubbles in human and rabbit sera.

Complement activation induced by air bubbles in rabbit and human sera was studied by measuring the generation of anaphylatoxin des-Arg-C5a. des-Arg-C5a was quantified by sandwich enzyme-linked immunosorbent assays based on neoepitope-specific anti-des-Arg-C5a monoclonal antibodies. Air bubbles were continuously introduced to serum via a calibrated microflowmeter, and the serum was incubated at 37 degrees C for 30 min. Air bubbles clearly generated increased amounts of des-Arg-C5a compared with corresponding levels in control serum, and a dose-dependent effect was also noted. Strong positive correlations between des-Arg-C5a concentrations in control sera and sera incubated with air bubbles at a flow of 0.5 ml/min were found. To study variation over time, serum was obtained at regular intervals from six rabbits and from six healthy humans during 66- and 196-day periods, respectively. A pronounced intraindividual variability over time was thus observed. The reason for the large variability is at present unknown. We conclude that the sensitivity of complement to activation by air bubbles is not an inherent, static feature of the complement system of an individual. Therefore single-point analysis of complement activation by air bubbles appears to be an inappropriate parameter by which to differentiate a "sensitive" or "insensitive" complement system between individuals.

Air↗
PubMed1993

Use of scale antibodies for the detection of antigens in psoriatic lesions.

Extractable IgG from psoriatic scale was purified, labelled with biotin and used in ELISA and immunofluorescence (IF) in an attempt to detect and localize prominent antigens in psoriatic scale extracts and in psoriatic lesions, respectively. Biotinylated immunoglobulins isolated from psoriatic scale from each of 5 patients were used. Scale extracts were fractionated on a Sephacryl S-300 column, and antigens detected by scale IgG were eluted in the void volume and at a Kav 0.55. The profile was very similar for each antibody preparation. Antigens recognized by serum IgGs from both healthy controls and psoriatic patients were detected in the void volume only. Antigens recognized by a rabbit antiserum against the psoriasis-associated antigen, pso p27 (6), were restricted to the fractions eluted at a Kav 0.55. Furthermore, the binding of scale IgG to the antigens eluted at Kav 0.55 was inhibited by purified pso p27 antigen. Two of the scale antibody preparations gave rise to a distinct fluorescence on skin biopsies from psoriatic lesions in indirect immunofluorescence. The antigens recognized were localized to a subfraction of dermal cells and in the endothelial lining of some of the dermal vessels. Double labelling with these scale antibodies and a rabbit anti-pso p27 antiserum showed that both antibody preparations bound to the same cells in the psoriatic lesions, while only a minority of these cells were recognized by a murine monoclonal antibody against human IgG. The observations described indicate that the pso p27 is a major antigen in the immune reactions in psoriasis.

Animals↗