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Biomedical subjects

C O Solberg

Publications and source records attributed to C O Solberg.

At least 19 recordsLinked to original sources

[Pneumococcal vaccine].

Streptococcus pneumoniae is a common cause of morbidity and mortality in children, immunodeficient individuals and elderly people. As antibiotic resistant strains become more prevalent, pneumococcal infections will become more difficult to manage. Pneumococcal vaccination is inexpensive, and serious side effects are rare. However, the efficacy and safety of the vaccine have been questioned, and the use of vaccination is limited. This article discusses factors to be considered when assessing the indications for pneumococcal vaccination. Immunisation together with a strict policy on the use of antibiotics are our most efficient means for preventing pneumococcal disease and spread of antibiotic resistant strains. Norwegian physicians are encouraged to use pneumococcal vaccine according to the present indications.

Bacterial Vaccines

Vertebral osteomyelitis at a Norwegian university hospital 1987-97: clinical features, laboratory findings and outcome.

Altogether 40 patients aged 13-91 y (average 58 y) with vertebral osteomyelitis were treated at the Bergen University Hospital between July 1987 and June 1997. All patients presented with back pain, 33 (83%) had vertebral tenderness, and 26 (65%) patients were febrile. The duration of symptoms before diagnosis was < 3 weeks in 13 patients, and from 3 to 16 weeks in the remaining 27 patients. C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) were elevated in 39 and 38 patients, respectively. Staphylococcus aureus was the most frequent cause of osteomyelitis followed by Streptococcus spp., Escherichia coli and Mycobacterium tuberculosis. Magnetic resonance imaging was superior to other radiological methods and demonstrated changes consistent with osteomyelitis in all 23 patients examined with this method. 35 patients survived. 18/35 surviving patients had pareses and 17 underwent surgery with drainage of abscesses or laminectomy. All 35 patients made a good recovery and only 3 patients experienced permanent pareses. The diagnosis of vertebral osteomyelitis is easily missed, and treatment is often delayed, particularly in the elderly in whom signs of sepsis may not manifest. However, persisting localized pain and tenderness over the spine together with elevated CRP and ESR should prompt the physician to consider vertebral osteomyelitis. Fever and leukocytosis may support the diagnosis, but may not always be present.

Adolescent

Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae from six Norwegian hospitals 1991-1992.

From August 1991 to February 1992, each of the six largest hospitals throughout Norway collected 84 to 107 consecutive blood culture isolates of Enterobacteriaceae, altogether 571 isolates. The distribution of various species and genera at the different hospitals was uniform; Escherichia coli being most prevalent (57-67%), followed by Klebsiella spp. (12-18%) and Proteus mirabilis (7-11%). Twenty-one and 4% of E. coli isolates were resistant to ampicillin and cefuroxime, respectively, and 11% of Klebsiella isolates were cefuroxime resistant. Five Enterobacter isolates and one Citrobacter isolate were resistant to ceftazidime, and one Salmonella isolate was resistant to imipenem. All isolates were susceptible to ciprofloxacin and tobramycin. These results were compared with the antibiotic consumption in each hospital region. Although hospitals in the regions with the highest consumption of ampicillin tended to have a higher percentage of isolates resistant to this agent, no significant differences were found. There was no significant difference between hospitals regarding prevalence of cefuroxime-resistant isolates.

Anti-Bacterial Agents

Serum levels of adhesion molecules and cytokines in patients with acute leukaemia.

The cytokine network and the adhesion molecule system are intercellular signal pathways. The cytokine effects are modulated in vivo by soluble cytokine antagonists, whereas the cell to cell contact mediated by adhesion molecules and their ligands may be blocked by the soluble forms of the adhesion molecules. The cytokine network is important for proliferation and cytokine secretion by acute leukaemia blasts, and membrane-bound adhesion molecules are important for blast interactions with neighbouring cells of the in vivo microenvironment. Both these signal systems are operative during the period of cytopenia following intensive chemotherapy for acute leukaemia. In the present review, we discuss the influence of disease status, chemotherapy and complicating infections on serum levels of cytokines and soluble adhesion molecules in acute leukaemia patients. We have demonstrated increased serum levels of both cytokines and cytokine antagonists in acute leukaemia patients with complicating bacterial infections during chemotherapy-induced cytopenia. Serum levels of the selectin adhesion molecules were decreased during bacterial infections in leukopenic patients compared to healthy individuals. In contrast, the intercellular adhesion molecule-1 response and the cytokine/cytokine antagonist responses were qualitatively similar to responses seen in previously healthy individuals with serious bacterial infections.

Acute Disease

Safety and efficacy of meropenem in patients with septicaemia: a randomised comparison with ceftazidime, alone or combined with amikacin.

Meropenem is a new broad spectrum carbapenem antibiotic which can be administered as monotherapy for serious infections. The efficacy and safety of meropenem was compared with that of ceftazidime (alone or in combination with amikacin) in 153 patients with septicaemia who were enrolled into identical, prospective, randomised studies. Forty-five patients with infections arising from the urinary or lower respiratory tracts were given either meropenem 500 mg or ceftazidime 250-1000 mg intravenously every 8 h; 108 patients with more serious infections were given meropenem 1 g or ceftazidime 2 g every 8 h +/- amikacin 15 mg/kg/day. Overall, 71 patients received meropenem, 47 ceftazidime and 35 ceftazidime plus amikacin. Comparable clinical response rates were achieved in the meropenem and ceftazidime/amikacin groups (92% vs 94% at the end of therapy respectively). Furthermore, a satisfactory bacteriological response was obtained in all evaluable patients. The most common pathogens isolated were Escherichia coli, Streptococcus pneumoniae and Pseudomonas aeruginosa. Relapse occurred in one patient in the ceftazidime/amikacin group, who had a mixed infection of E. coli and P. aeruginosa. There were no relapses in the meropenem group. Both treatments were well tolerated and only one patient had to withdraw from the trial because of an adverse effect (rash associated with ceftazidime). In conclusion, these data confirm that meropenem monotherapy is well tolerated and is as effective as ceftazidime (alone or combined with amikacin) in the empirical treatment of septicaemia. It should prove to be a useful addition to the drugs currently available for this life-threatening disease.

Adult

Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst.

Porins are trimeric proteins that constitute water-filled pores that allow transmembrane diffusion of small solutes through the outer membrane layer of gram-negative bacteria. The porins are capable of inserting into the membranes of eucaryotic cells, and in the present study we have examined the in vitro effects on neutrophil functions of the following purified porins: meningococcal outer membrane protein classes 1 and 3 and gonococcal outer membrane protein 1B (P1B). The neisserial porins inhibited human neutrophil chemoattractant-induced actin polymerization and degranulation of both primary and secondary granules. The neutrophil expression of immunoglobulin G (IgG) Fc receptors II (Fc gamma RII; CDw32) and III (Fc gamma RIII; CD16), as well as the activation-dependent downregulation of Fc gamma RIII, were reduced by the meningococcal and gonococcal porins. The neisserial porins impaired the upregulation of complement receptors 1 (CD35) and 3 (CD11b) and inhibited the phagocytic capacity of neutrophils, as evaluated by the uptake of meningococci (strain 44/76) in the presence of patient serum containing known amounts of IgG against meningococcal porins. The porins also primed neutrophils to increase their intracellular hydrogen peroxide production in response to FMLP, whereas no such priming was observed if the neutrophil protein kinase C was stimulated directly with phorbol myristate acetate. The neisserial porins influenced neutrophil functions in a time- and concentration-dependent manner. The meningococcal class 1 outer membrane protein and the gonococcal P1B tended to alter neutrophil functions more than the meningococcal class 3 protein. Thus, the neisserial porins inhibited human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but primed the neutrophils to increase their oxidative burst. It remains to be determined whether these in vitro observations reflect mechanisms that may be of importance for the interaction between neutrophils and Neisseria species in vivo.

Actins

[Infection with group A Streptococcus].

In the last 8-10 years, the prevalence of severe group A streptococcus (GAS) infections such as bacteremia, erysipelas, necrotizing fasciitis and puerperal fever has increased significantly in industrialized countries. Shock, acute respiratory distress syndrome and multiorgan failure have been common features, and the attributable mortality has been as high as 30 per cent. The majority of infections have occurred in otherwise healthy adolescents and adults, and the GAS strains have been predominantly M types 1 and 3, which produce pyrogenic exotoxins, indicating an increased virulence of these strains. The article reports on the prevalence, pathogenesis, clinical features and treatment of severe GAS infections.

Adolescent

[Use of antimicrobial agents in Norway 1980-92].

Use of systemic antimicrobial agents in Norway shows a moderate increase from 1980 to 1992, from 13.5 to 16.9 defined daily doses (DDDs) per 1,000 inhabitants per day. Comparing the Nordic countries, the use of these drugs is second lowest in Norway, after Denmark. In relative terms the use of tetracyclines is highest in Norway. Use of co-trimoxazole is also relatively high, while use of macrolides is low. The share of penicillin V and G is highest in Sweden. Several new and important antimicrobial agents have been introduced on the Norwegian market during the period, while almost as many have been withdrawn. Penicillin V and G constitutes the main subgroup. However, the use of tetracyclines is almost as high, for a short period in fact higher. Taking into account the development of drug resistance and adverse events, it is recommended that use of tetracyclines and co-trimoxazole be reduced, mainly to the advantage of penicillins. The use of cephalosporins seems to be reasonable, but penicillins should be considered more often as an alternative. The use of antimycotic and antiviral drugs is low in terms of DDDs. In 1992 the cost of antimicrobial agents for systemic use was in 1992 approx. NOK 400 million, retail price. The largest subgroup, cephalosporins, constituted almost 20%, as against only 2% of DDDs. Antimicrobial agents represent a substantial part of the total drug budget in hospitals. A shift from expensive to cheaper alternatives should be considered as a routine. Moreover, an optimal change from parenteral to oral administration could help to reduce costs.

Anti-Bacterial Agents

Bloodstream infections at a Norwegian university hospital, 1974-1979 and 1988-1989: changing etiology, clinical features, and outcome.

All episodes of bloodstream infection in patients admitted to a Norwegian university hospital in 1974-1979 and in 1988-1989 were analyzed; altogether, there were 1,447 episodes involving 1,286 patients, and 54.3% of all episodes were hospital-acquired. The incidence of bloodstream infection increased between the two periods studied from 4.26/1,000 admissions to 8.71/1,000. Crude mortality rates were 27.6% and 18.8% and attributable mortality rates were 12.3% and 6.9% in the first and second periods, respectively. Patients > 60 years of age accounted for more than half of the bloodstream infections; mortality in this group was significantly higher than that among younger patients (31.4% vs. 13.9%). The frequency of isolation of Enterobacteriaceae decreased from 48% in the first period to 34% in the second, while the rate of isolation of coagulase-negative staphylococci increased from 6.5% to 16.9%. The shift in etiology may be explained in part by the occurrence of significantly more bloodstream infections related to intravascular devices, endocarditis, and skin and wound infections and of significantly fewer episodes related to abdominal or genitourinary disease in the second than in the first period. Almost all isolates of Enterobacteriaceae were susceptible to newer cephalosporins and aminoglycosides. In 1974-1979, 96 (69.1%) of 139 patients with septic shock died; in 1988-1989, the figure was 35 (52.2%) of 67 patients (P = .019). Clinical factors predictive of an adverse outcome were septic shock (odds ratio for first/second period, 12.7/4.6), intensive care treatment (not significant/10.6), malignant disease (4.6/2.6), any underlying disease (4.2/not significant), diabetes mellitus (3.6/not significant), age of > 60 years (not significant/3.0), and pulmonary source of infection (not significant/2.8).

Adolescent

A longitudinal study of phagocyte function in HIV-infected patients.

OBJECTIVE: To study the influence of HIV infection on phagocyte function. To date, the results of phagocyte function studies in HIV-infected patients have been contradictory. This is the first longitudinal study of these functions in HIV infection. DESIGN: We followed 50 individuals with HIV infection for 2-51 months (mean, 28 months) and examined polymorphonuclear leukocyte (PMNL) and monocyte functions at intervals of 0.5-1 years. METHODS: PMNL random migration and chemotaxis were assessed using an under-agarose method, and PMNL and monocyte oxidative metabolism by chemiluminescence production during phagocytosis of opsonized zymosan. RESULTS: PMNL random migration and chemotaxis were impaired at entry into the study by 15 and 19%, respectively. After 3 years the reduction was 35 and 32%, respectively. The mean chemiluminescence production by PMNL was reduced by 6% at entry into the study. After 4 years a decrease of 18% was observed. The decrease in PMNL function was most marked in patients with lymphadenopathy syndrome or AIDS. No significant change in monocyte chemiluminescence production was detected at any time during the study. CONCLUSIONS: A distinct and progressive decrease of PMNL function occurs during HIV infection. This may contribute to increased susceptibility to opportunistic infections in HIV-infected patients. For monocytes, chemiluminescence production is not influenced by HIV infection.

Adult

Isoprinosine stimulates granulocyte chemiluminescence and inhibits monocyte chemiluminescence in vitro.

Isoprinosine may delay disease progression in human immunodeficiency virus infection, presumably through modulation of lymphocyte function. However, the influence of isoprinosine on phagocyte function is largely unknown. This study describes the effects of isoprinosine and azidothymidine on phagocyte chemiluminescence and migration. Incubation with isoprinosine concentrations of 250 micrograms/ml and above increased the chemiluminescence of granulocytes. Random migration of granulocytes was decreased at isoprinosine concentrations of 50 micrograms/ml and higher, but chemotaxis was not affected. Azidothymidine exerted no effect on the chemiluminescence or migration of granulocytes. For monocytes, luminol-enhanced chemiluminescence was reduced at isoprinosine concentrations of 250 micrograms/ml and above, whereas migration was not affected. These findings suggest that the immunomodulatory properties of isoprinosine may extend to phagocytic cells. This may be of significance in the treatment of immunodeficiency states.

Cell Movement

Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease.

We have determined the amounts of specific anti-class 1 outer membrane protein antibodies in sera from 25 patients during the course of systemic meningococcal disease, using purified class 1 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay. The class 1 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 3 and class 4 outer membrane proteins. Specific anti-class 1 (serosubtype P1.7,16) outer membrane protein immunoglobulin G (IgG) antibody levels increased significantly in 12 patients (12 of 25; 48%), regardless of the serotype of the infecting strain, indicating that the antibodies reacted in part with epitopes not determined by the monoclonal antibodies used for serotyping. Most patients had low levels of anti-class 1 IgG antibodies during the acute illness. The antibody levels peaked during the second week of disease and returned to near baseline levels in sera collected 6 weeks to 12 months after the onset of the disease. The majority of the specific anti-class 1 IgG antibodies bound to surface-exposed epitopes on whole bacteria and belonged to the IgG1 and IgG3 subclasses. Anti-class 1 IgA and IgM antibodies were not detected in any of the patient sera. Prior to disease, seven patients had been immunized with a meningococcal outer membrane vesicle vaccine developed from strain 44/76 (P1.7,16). None of these patients was infected with meningococcal strains containing class 1 protein homologous or partly homologous to that of the vaccine strain, indicating serosubtype-specific protection. The highest anti-class 1 IgG antibody peak levels were seen in immunized patients infected with strains of heterologous serotype, suggesting an anamnestic response. However, these patients were not protected from meningococcal disease after immunization.

Adolescent

Cross-reacting serum opsonins to meningococci after vaccination.

The opsonic activity of sera from healthy volunteers immunized with an outer membrane vesicle vaccine prepared from a Neisseria meningitidis (class 3, 44/76, B:15:P1.7,16), characteristic of the present Norwegian epidemic, has been examined. A marked increase in the phagocytosis of class 3 and nontypeable strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of postvaccination sera. Sera from vaccinees also caused a significant increase in leukocyte oxidative metabolism as measured by luminol-enhanced chemoluminescence during phagocytosis of class 3 and nontypeable meningococci. An increase in serum opsonins cross-reacting with class 2 (type 2a) meningococci of different serogroups was not observed, suggesting that future meningococcal outer membrane vesicle vaccine preparations should contain both class 2 and class 3 porins in geographic areas where both class 2 and class 3 strains cause disease.

Antibodies, Bacterial

Cross-reacting serum opsonins in patients with meningococcal disease.

We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence. A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera. Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence. The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes.

Adolescent

Negative selection of human monocytes using magnetic particles covered by anti-lymphocyte antibodies.

We have developed a standardized procedure for the isolation of monocytes from peripheral blood by negative selection using magnetic polymer particles coated with monoclonal antibodies against T and B lymphocytes. The average purity of the monocyte suspension was 85%, and monocyte recovery was 72% from Ficoll-Hypaque gradient separated mononuclear cells and 32% from whole blood. In a lucigenin enhanced chemiluminescence assay there was no significant difference between cells separated immunomagnetically and those separated on a gradient. Nor did electron microscopy show any significant difference in morphology between such monocytes. Negative selection using magnetic polymer particles is an efficient method for the separation of monocytes with intact morphology and function as measured by chemiluminescence.

Antibodies, Monoclonal