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Biomedical subjects

B Haneberg

Publications and source records attributed to B Haneberg.

At least 55 records · Page 3Linked to original sources

Case fatality of meningococcal disease in western Norway.

In the period 1976-84, 211 patients hospitalized with meningococcal disease were examined for possible relation between various epidemiological parameters and fatality. The peak incidences were in the age groups 0-4 and 13-18 years, with teenage girls peaking 2 years ahead of the boys. The overall case fatality rate was 8.5%. In septicemic patients (without meningitis) hypotension and/or ecchymoses on admission correlated strongly with a poor prognosis. Most deaths occurred during the months of March and November, and none during the summer months. There was a significant clustering of deaths among patients admitted during the morning hours, probably due to delayed diagnosis and treatment during the night. Since almost all patients who died had skin bleedings on admission, frequent examination of the skin in cases with acute unexplained fever might have saved lives.

Adolescent↗

Factors important for the measurement of chemiluminescence production by polymorphonuclear leukocytes.

Chemiluminescence (CL) production by phagocytosing polymorphonuclear leukocytes (PMNLs) was measured by an automatic photoluminometer with built-in mixing and temperature controls. Agitation of the vials with PMNLs and opsonized zymosan particles influenced both the lag time and the CL production. Maximal production was obtained by continuous mixing of the samples, the reaction peak occurring within 6 min. Increasing the temperature from 20 to 40 degrees C also increased the CL production, and in further experiments 37 degrees C was used. Aggregation of the PMNLs was avoided by washing the cells in PBS containing gelatin 1 g/l. Glucose, Ca2+ and Mg2+ in the final reaction mixture were necessary for maximal CL responses. The measurements of CL per s up to 4 min, the peak CL value, or the integral below the CL curve up to 6 min were all linearly proportional to the number of PMNLs in the reaction mixture. Since the lag time and the time before reaching peak CL may vary, the integral below the curve up to 6 min was chosen as the mode of CL measurement. On repeated measurements the coefficient of variation was 6.3%. The mean CL integral value for PMNLs from 14 healthy individuals was 205 +/- 19 mVs, indicating a good reproducibility of the standardized assay.

ABO Blood-Group System↗

Influence of tetracyclines and light on the release of lysozyme from human granulocytes and monocytes.

Doxycycline inhibited the release of lysozyme from human granulocytes and monocytes exposed to non-opsonized zymosan particles. This effect was more marked for granulocytes than for monocytes. Oxytetracycline, however, did not influence the release. The difference between the drugs can be explained by differences in their lipid solubilities. The divalent cation chelator, EDTA, also reduced the release of lysozyme from leukocytes exposed to non-opsonized zymosan. Accordingly, the selective release of lysozyme from human leukocytes is divalent cation dependent. The inhibition of release by doxycycline is most likely also due to binding of these ions. When the cells were exposed to UVA light in the presence of doxycycline, the inhibition of lysozyme release was potentiated. Using irradiated cells, maximal inhibition was obtained at 20 micrograms doxycycline/ml. However, it is not clear whether these results have clinical relevance.

Doxycycline↗

The excretion of IgE with feces from healthy individuals and from others with allergy and diseases affecting the intestinal tract.

In this study we looked for the occurrence of immunoglobulin E (IgE) in feces from healthy individuals and determined the total daily excretion and day-to-day variation in IgE in feces from patients with allergy, as well as the correlation between concentrations of IgE in small samples of feces and the total amounts of IgE in feces collected over a longer period. Concentrations of IgE in extracts of small samples of dry feces correlated well with the total daily amounts of IgE in feces collected over a 3-day period. Thus, single small samples of feces can be used to measure the excretion of IgE with feces at that time. In 3 children, studied over a 5-week period, the IgE excretion varied somewhat from one day to another, but was largely within a certain range of concentrations. Addition of trypsin inhibitor to fresh feces had no influence on the IgE concentrations of the resulting fecal extracts. Less than 10% of 88 presumably healthy infants, children, and adults had detectable IgE in their feces, while 21 of 40 children with various kinds of allergy had measurable fecal IgE. Only 3 of 13 individuals who were suffering from infectious acute gastroenteritis had IgE-positive fecal extracts. This was also the case for 6 of 25 adult patients in clinical remission of ulcerative colitis or Crohn's disease. Seven of 14 adult patients with chronic pancreatitis had measurable IgE in feces, and the concentrations were up to ten times the upper limit of IgE found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Influence of fever temperatures and of some cytoactive drugs on in vitro lysozyme release from monocytes and granulocytes.

The selective in vitro release of lysozyme from human monocytes and granulocytes was not greatly influenced by temperatures above 37 degrees C and up to 40 degrees C. The release was markedly inhibited by preincubation with phenylbutazone, oxyphenylbutazone, colchicine and vincristine. A water-soluble hydrocortisone complex also inhibited lysozyme release, but at high concentrations, lysis of the cells occurred. Although methotrexate had a weak inhibiting effect, no appreciable influence on release was observed with cyclophosphamide or cytarabine. Thus, release of lysozyme from blood leukocytes is likely to be dependent on cellular functions involving the stability of both microtubules and membranes.

Body Temperature↗

The influence of antimicrobial agents on macrophage-associated Staphylococcus aureus.

Macrophages obtained by culturing human blood monocytes were incubated with Staphylococcus aureus for phagocytosis to occur and exposed to gentamicin, rifampin, clindamycin or trimethoprim/sulphamethoxazole. The macrophage-associated bacteria were protected against gentamicin at low concentrations (1 mg/l) and trimethoprim/sulphamethoxazole. However, high concentrations of gentamicin and clindamycin reduced the number of bacteria, indicating that these drugs penetrated into human macrophages and killed phagocytosed bacteria. Rifampin, even at low concentrations (0.5 mg/l), caused a marked reduction in macrophage-associated bacteria, implying that the drug penetrated into the phagocytes and retained its effect in the cells most effectively.

Anti-Bacterial Agents↗

Immunoglobulin E in feces from children with allergy. Evidence of local production of IgE in the gut.

Immunoglobulin E (IgE) was found by a double antibody radioimmunoassay technique (PRIST) in extracts of feces from 21 of 40 children with different kinds of allergy. 15 of the 22 children with gastrointestinal allergy and atopic dermatitis, but only 6 of the 17 patients with hay fever and/or bronchial asthma had detectable IgE in the extracts. The patients with gastrointestinal allergy also had the highest concentrations of fecal IgE, and the concentrations in feces did not correlate with the corresponding serum IgE levels. Furthermore, the presence of IgE in feces correlated with specific IgE antibodies in serum, measured as the sum of RAST classes to the food allergens wheat, fish, cow's milk and egg-white. IgE may therefore have been produced locally in the gut as a result of stimulation by food allergens. Since the concentrations of IgA in feces were also high in many children with allergy, and since some possibility of a positive correlation with high IgE concentration seemed to exist, the stimuli for local production of IgE and IgA may be interrelated.

Adolescent↗

Detection of immunoglobulin E in feces by immunoprecipitation, and characterization of associated non-immunoglobulin precipitins.

All concentrated human fecal extracts tested formed precipitates in double immunodiffusion with goat antiserum to IgE, as well as with normal goat sera. However, no such precipitates were formed by fecal extracts and rabbit sera. IgE precipitates obtained with both goat and rabbit antisera to IgE showed reactions of non-identity with the former precipitates which seemed to represent complexes of trypsin or chymotrypsin in feces and an alpha-protein in goat sera. This alpha-protein, which was responsible for the non-immunoglobulin precipitations, was different from human alpha 1-antitrypsin. The trypsin-like components in feces had low molecular weights, and might represent degradation products of trypsin or chymotrypsin. After using a second labelled antiserum, precipitates between rabbit antiserum to IgE and extracts of feces could be visualized by means of autoradiography. They were seen in fecal extracts in which IgE could also be determined by a double-antibody paper radioimmunoassay technique (paper radio immunosorbent test; PRIST). Since the concentrations measured by a radioactive single-radial immunodiffusion method correlated to some extent with the PRIST concentrations, the latter precipitates were likely to represent IgE in feces.

Animals↗

Fragments of IgE antibodies in human feces.

The gel filtration profile of immunoglobulin E (IgE) in extracts of feces from 2 children was compared with IgE myeloma protein which had been exposed to proteolytic digestion by chymotrypsin. The peak of the chymotrypsin-digested IgE myeloma protein was found to be similar to that of fecal IgE after an elution volume between those of albumin and myoglobin, corresponding to a molecular weight of approximately 40,000 daltons. In the fractions where the peak of fecal IgE was found, no evidence for the presence of specific IgE antibodies (measured by RAST) could be detected. Fecal IgE could be purified by using an immunosorbent column to which rabbit antihuman IgE was coupled. Sufficient amounts of fecal IgE could thus be obtained and used in autoradiographic experiments. The IgE-containing fractions could also be detected with 125I-labelled second antibodies to visualize the IgE precipitates.

Antibodies↗

The latency of serum acute phase proteins in meningococcal septicemia, with special emphasis on lactoferrin.

Serum lactoferrin concentrations were elevated in almost all children with meningococcal septicemia, in whom the disease had been clinically apparent for less than 18 hours, while the concentrations were normal or only moderately elevated in patients who had had the disease longer before being admitted. Concentrations of C-reactive protein (CRP) were markedly elevated, even with a time lapse of less than six hours, making this the most suitable parameter for the early diagnosis of severe meningococcal infection. Following an operative injury on children the lactoferrin concentrations changed very little. More than six hours after an operation, however, a marked increase in CRP-values was observed, possibly indicating differentiation of this response from that of bacterial infection. The concomitant study of serum alpha 1-antitrypsin, alpha 1-antichymotrypsin, orosomucoid and haptoglobin did not uncover results of great significance with regard to early changes.

Acute Disease↗

In vitro release of lysozyme from monocytes and granulocytes.

When exposed to zymosan or latex particles or heat-inactivated staphylococci, freshly prepared human blood monocytes and granulocytes rapidly released a large fraction of their lysozyme content. Within 24 hours the total lysozyme activity in the monocyte suspensions tripled, while it doubled in the granulocyte suspensions, indicating synthesis of the enzyme following release. The monocytes in particular seemed to release and synthesize lysozyme without any other stimulus than contact with lymphocytes and the tube walls. Potassium caseinate in solution did not influence the lysozyme release. Myeloperoxidase and beta-glucuronidase, which in the granulocytes are kept in lysosomal fractions separate from most of the lysozyme, were neither released nor synthesized to a significant degree. Moreover, the minute amount of lactate dehydrogenase released indicated that the lysozyme release was not the result of cell lysis. Accordingly, the monocytes, which are not already stimulated by adherence to nonphagocytosable surfaces, are capable of selective enzyme release similar to that of the granulocytes.

Glucuronidase↗

Lactoferrin in relation to acute phase proteins in sera from newborn infants with severe infections.

Serum lactoferrin concentrations were elevated in 22 out of 49 newborn infants with suspected and verified severe bacterial as well as viral infections, suggesting that this protein resembled an acute phase reactant. In the infants suspected of having septicemia, high concentrations of C-reactive protein appeared to indicate a severe bacterial infection. Like lactoferrin, however, haptoglobin, orosomucoid, alpha 1-antitrypsin and alpha 1-antichymotrypsin discriminated only poorly or not at all between infants with severe bacterial infections and those in which such infections were unlikely. Thus, serum CRP concentrations remained the most valuable of the acute phase reactants tested as an aid in ruling out septicemia in the neonatal period.

Acute Disease↗

Serum concentrations of vitamin D metabolites in exclusively breast-fed infants at 70 degrees north.

The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 7 1/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (less than 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations, while the others maintained 1,25-(OH)2D levels within normal limits. 24,25-(OH)2D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phosphatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.

Alkaline Phosphatase↗

The influence of harvesting intervals on chemiluminescence and enzyme activities of rat peritoneal leukocytes.

Rat leukocytes were obtained from the peritoneal cavity by stimulation with potassium caseinate. The chemiluminescence response of the polymorphonuclear leukocytes exposed to opsonized zymosan was influenced by the interval between instillation of caseinate and harvesting of the cells. With intervals increasing from four to 72 hours, the maximum activity was reached after 24 hours. The myeloperoxidase activity of all the leukocytes together increased gradually up to 72 hours after instillation of caseinate. After exposure to zymosan particles, only a negligible fraction of this enzyme was released from the cells. On the other hand, the lysozyme activity was highest in cells harvested early, and a large fraction of this enzyme was also released from these cells. The findings emphasize the importance of standardized conditions for stimulation and harvesting of rat peritoneal leukocytes.

Animals↗

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes.

When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 micrograms/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.

Humans↗

Human opsonins to meningococci after vaccination.

Two groups of volunteers were immunized with either a serogroup A plus C meningococcal polysaccharide vaccine or a combined serogroup B polysaccharide-serotype 2 protein vaccine. Serum opsonin responses were measured by chemiluminescence of polymorphonuclear leukocytes exposed to opsonized live meningococci. Two of the six volunteers immunized with the A plus C vaccine had an increase in serum opsonins to group A meningococci, four responded to group C meningococci, and none to group B meningococci. Five other volunteers who were immunized with the combined group B polysaccharide-serotype 2 protein vaccine responded with an increase in serum opsonins to group B meningococci of two different protein serotypes, as well as to a group C-serotype 2 meningococcal strain. Although no booster effect was observed after a second dose of the combined vaccine, both the polysaccharide and the protein components appear to be able to stimulate an opsonin response.

Bacterial Vaccines↗

Immunoglobulin E in extracts of feces from children.

Immunoglobulin E (IgE) was demonstrated by a double antibody radioimmunoassay technique (PRIST) in 5 of 17 unconcentrated fecal extracts from children. Four of the PRIST-positive extracts also had measurable levels of IgE determined by an enzyme-linked immunosorbent test (Enzygnost IgE). However, using a competitive antibody radioimmunoassay technique (RIST), IgE was found in all unconcentrated fecal extracts. The RIST-IgE levels of the extracts were higher and did not correlate to IgE measured by the other methods, nor to the IgE in serum from the same children or to the manifestation of allergy. On the other hand, 4 of the 5 children with measurable PRIST-IgE levels, and 3 of the 4 children with detectable Enzygnost IgE concentrations in the extracts, had elevated serum IgE as well as a history of allergy. Gel filtration studies indicated that IgE determined by the PRIST and Enzygnost IgE methods had been degraded to fragments of lower molecular weight than that of albumin. This study also suggests that the IgE in feces measured by the RIST method is overestimated due to the influence from nonspecific substances of high molecular weight.

Child↗