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Biomedical subjects

C O Solberg

Publications and source records attributed to C O Solberg.

At least 91 records · Page 5Linked to original sources

Factors influencing human polymorphonuclear leukocyte chemiluminescence.

Divalent cations (Mg2+, Ca2+) regenerated chemiluminescence (CL) of zymosan-stimulated human polymorphonuclear leukocytes (PMNs) abolished by 0.1 mM EGTA. Phenol red, erythrocytes and free haemoglobin reduced CL. To obtain maximal CL response, the reaction mixture should contain small amounts of protein and glucose. High protein concentrations reduced CL. The test had a pH optimum of 7.1. With respect to stability, however, the most favourable pH was 7.4. The CL response was highly temperature-dependent, and expressed as the initial rate constant of the CL time curve it increased linearly with increasing temperatures from 20 to 37 degrees C. Several factors influence the CL response by human PMNs and test procedures should be standardized.

Blood Platelets↗

Polymorphonuclear leukocyte function in bacterial and viral infections.

Chemiluminescence (CL) production by polymorphonuclear leukocytes (PMNLs) was examined in 63 patients with bacterial infections and 63 healthy controls. The production was significantly higher in the patients (mean +/- standard error = 134.5 +/- 5.0 X 10(3) cpm) than in the controls (118.9 +/- 2.5 X 10(3) cpm; p less than 0.05). In 38 patients CL values were within the normal range and in 19 patients above. CL production below that of any control occurred in 6 patients: 3 (of 4) with staphylococcal endocarditis, 2 (of 4) with pneumococcal meningitis and 1 with salmonella septicaemia and osteomyelitis. PMNL hexose monophosphate shunt activity as measured by glucose metabolism correlated with CL production. Patients with low CL production more often had large numbers of juvenile and immature myeloid cells in the peripheral blood than patients with normal or high CL values. 3/6 patients with low CL values died, 2/38 with normal and 0/19 with high values. Directed and spontaneous PMNL migration was examined in 39 of the 63 patients with bacterial infections. 13 patients had PMNLs with higher directed and 16 with higher spontaneous migration capacity than their corresponding controls. The remaining patients had PMNLs with lower migration capacity. 2 of the 39 patients died. Each had PMNLs with low migration capacity. CL production by PMNLs was examined in 16 patients with viral infections and 16 healthy controls. The production was significantly lower in the patients (mean +/- standard error = 105.5 +/- 6.6 X 10(3) cpm) than in the controls (129.1 +/- 5.3 X 10(3) cpm; p less than 0.01). 15 patients had lower values than their corresponding controls. The PMNL migration capacity was also lower in the patients. These findings indicate that the majority of patients with bacterial infections have PMNLs with normal or increased function. However, some patients have reduced PMNL function and this reduction may contribute to a fatal outcome of the disease. Patients with viral infections usually have reduced PMNL function.

Adolescent↗

Pathogenesis of septicaemia: aspects of cellular defence mechanisms.

In the secondary defence line against bacterial invasion, the phagocytic cell systems serve as effector mechanisms of specific and unspecific immunity. In bacterial infections including septicaemia the outcome of the host-parasite interaction is determined by the ability of the mono- and polymorphonuclear phagocytes to recognize and kill the invading organisms in the presence of humoral and lymphocytic factors. The quantitative aspects of phagocytic deficiency is well recognized, in general and the risk of bacterial infection in a given patient is related directly to the duration of granulocytopenia and inversely to the number of circulating granulocytes. Reduced numbers of monocytes or, as in the splenectomized patient, lack of tissue macrophages may also add to increase suseptibility to infection with certain bacteria. Functional defects in phagocytosis in the presence of normal peripheral neutrophil and monocyte counts become increasingly important with the sophisticated procedures of modern medicine. In reviewing the functional capacity of the phagocytes it is convenient to consider four interrelated phases: 1) the vascular phase characterized by amrgination, adherence and diapedesis of the cells, 2) the chemotaxis of the directed movement of the cells to site of microbial invasion, 3) the phagocytosis or ingestion of microorganisms, and 4) the cellular factors involved in the killing and decomposition of the microorganisms. Enhanced susceptibility to infection has been related to defects in any of these functions, and the basic types of inborn or acquired abnormalities are reviewed. The problems of iatrogenic defects in antimicrobial host resistance may, hopefully, be reduced by an increasing knowledge in pathophysiology and the various steps involved in the cellular defence mechanisms.

Chemotaxis↗

Porphyrin-induced photodamage to isolated human neutrophils.

Human neutrophils were irradiated with light at 340-380 nm in the presence of low concentrations of protoporphyrin or uroporphyrin. At increasing light doses or increasing concentrations of protoporphyrin, the neutrophils rapidly lost the ability of locomotion. Also, neutrophil chemiluminescence and hexose-monophosphate shunt activity rapidly declined. An early event was leakage of endogenous K(+) followed by lactate dehydrogenase and at a later stage leakage of particle-bound acid phosphatase. A number of cellular enzymes were inactivated, the susceptibility to inactivation decreased in the order: succinate dehydrogenase greater than lactate dehydrogenase greater than glutamate dehydrogenase greater than acid phosphatase. Uroporphyrin had no effect on neutrophil functions, leakage of K(+), or cellular enzymes. The results suggest that photodamage to the plasma membrane and the mitochondria are earlier events than photodamage to lysosomes.

Humans↗

[Infections].

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Communicable Disease Control↗

Chemiluminescence by polymorphonuclear leukocytes from patients with active bacterial infection.

Polymorphonuclear leukocytes of 18 patients during 19 episodes of active bacterial infection produced increased chemiluminescence (mean +/- standard error [SE], 56.3 +/- 4.4 X 10(3) cpm) when the production was compared to that of 29 uninfected controls (35.3 +/- 2.4 X 10(3) cpm; P less than 0.01). Chemiluminescence production remained increased with persistent infection but fell to the levels of controls with appropriate therapy. Phagocytic uptake as determined with radiolabeled bacteria was increased, and chemotactic responsiveness was markedly enhanced in the patients (mean index +/- SE, 260 +/- 51) when these responses were compared with those of controls (77 +/- 18). Chemiluminescence and chemotactic activity correlated in the patients with bacterial infection (r = 0.76), but one function did not appear to depend upon the intactness of the other. The ratio of cyclic guanosine 3',5'-phosphate to cyclic adenosine 3',5'-hosphate in the polymorphonuclear leukocytes of patients with infections (mean +/- SE, 0.102 +/- 0.0008) was also significantly higher than in controls (0.067 +/- 0.007). These data indicate that the polymorphonuclear leukocytes of the majority of patients with active bacterial infection are in an activated state both functionally and metabolically.

Adolescent↗

Group B meningococcal opsonins in serum measured by polymorphonuclear leukocyte chemiluminescence.

Serum opsonic activity against a strain of group B meningococci was measured by the initial increment in polymorphonuclear leukocyte chemiluminescence. Chemiluminescence was markedly enhanced by serum and was dependent upon both thermostable and thermolabile factors. It was higher in convalescent sera from patients with meningococcal disease than from other patients and normal controls. Absorption of sera with the homologous strain substantially decreased the opsonic activity. Convalescent serum from a patient with group C meningococcal pericarditis showed high opsonic activity towards a group B meningococcal strain. A convalescent serum showed significantly higher activity towards its homologous group B strain than towards another group B meningococcal strain. As measured by chemiluminescence, properties besides group specificity are of importance in opsonization of meningococci. The simplicity and precision of the chemiluminescence measurements seem to offer an improved tool for the study of meningococcal disease immunology.

Humans↗

Susceptibility of 4410 clinical isolates to doxycycline.

In an 1100-bed hospital where doxycycline has been widely used, the susceptibility to doxycycline of 4410 clinical isolates was examined. Ninety-one and 80.8 per cent of the Staphylococcus aureus and Haemophilus influenzae strains, respectively, were susceptible to 1 mg doxycycline/l. Seventy-four per cent of the Escherichia coli and 81.7 per cent of the Klebsiella strains were inhibited by 4 mg/l. The Enterobacter and Enterococcus strains were less susceptible. Nearly all Proteus mirabilis isolates were resistant. The results are comparable to those of other studies.

Bacteria↗

High dose netilmicin therapy of severe or chronic infections.

Sixteen patients with chronic or recurrent urinary tract infections, 14 with septicaemia, 2 with salmonellosis, 2 with pneumonia and 1 with acute mastitis were treated with 200 mg (2.2-3.6 mg/kg) netilmicin intramuscularly every 8 hours for 7-10 days (mean 8.8 days). 28 patients were cured, 5 showed marked improvement and 2 patients with septicaemia and severe underlying diseases failed to respond to treatment. The bacterial isolates were inhibited by 4.0 mg netilmicin/l or less. Antibiotic serum level determinations were performed in 32 patients. Mean serum concentrations of netilmicin 1 and 8 hours after injection were 12.6 and 2.0 mg/l respectively in 27 patients with normal serum creatinine levels. In 5 patients with elevated serum creatinine, mean peak and trough values were 21.5 and 5.8 mg/l, respectively. Mean netilmicin concentrations in serum and skin blister fluid obtained from 4 patients were equal 2-3 hours after injection, indicating appropriate tissue penetration. Nephrotoxicity occurred in 2 patients. Ototoxicity was not demonstrated. Netilmicin appears to be an effective and safe drug in the treatment of a variety of bacterial infections.

Adult↗

Pivmecillinam treatment of chronic urinary tract infection.

Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections.

Administration, Oral↗

Influence of phenylbutazone on leukocyte chemiluminescence and function.

The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular killing of bacteria has been examined. A marked reduction of chemiluminescence and intracellular killing of bacteria was observed. The effect on phagocytosis was less pronounced. High drug concentrations nearly abolished light emission, and concentrations equivalent to those obtained in plasma during therapy caused a 25--30% reduction. The effect occurred within less than 10 minutes. No permanent effect upon resting cells was observed. Phenylbutazone reduced the effect of sodium azide on leukocyte chemiluminescnece, indicating that the drug might also inhibit myeloperoxidase dependent chemiluminescnece. Whether these impairments of leukocyte function also take place in vivo resulting in enhanced susceptibility to infection remains unknown.

Azides↗

Susceptibility of 327 clinical isolates to netilmicin.

Netilmicin, a semisynthetic derivative of sisomicin, was tested against 327 isolates of Staphylococcus aureus, Pseudomonas aeruginosa and Gram-negative enteric bacilli. Seventy-two per cent of the isolates were inhibited at a concentration of 0.5 microgram netilmicin per ml, and 93% of the isolates were susceptible to 4 microgram per ml or less. The MICs of netilmicin and gentamicin for 24 Providencia and 38 Pseudomonas isolates were compared. The activity of netilmicin closely paralleled that of gentamicin, 46% of the Providencia isolates and 32% of the Pseudomonas isolates not being inhibited by 4 microgram per ml of either drug.

Enterobacteriaceae↗