Bjørn Haneberg

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.

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.

Immunoglobulin E in Feces from Children with Allergy

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, cows 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.

ANTIBODIES TO CYTOMEGALOVIRUS AMONG PERSONNEL AT A CHILDREN'S HOSPITAL

Abstract. Haneberg, B., Bertnes, E. and Haukenes, G. (Department of Paediatrics and Department of Microbiology, University of Bergen, Norway). Antibodies to cytomegalovirus among personnel at a childrens hospital. Acta Paediatr Scand, 69:407, 1980.—Among 161 individual personnel at Childrens Hospital, serum complement fixing antibodies were found more frequently (77%) in those who were in close contact with the patients than (39%) in those with less contact. This difference was most pronounced in the young age group. Most (80%) of the personnel at an age of 30 years or older, were seropositive. The results indicate that young personnel, working in close contact with infants and children in hospital, are at great risk of acquiring cytomegalovirus infection. Student nurses, being exposed to these patients only for a few weeks, also were at risk of being infected. Seronegative pregnant women, working in a childrens hospital, should therefore take measures to protect themselves from close contact with the patients since virus excretion occurs frequently, even without clinical signs of CMV‐infection.

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.

CLINICAL ASSESSMENT OF GESTATIONAL AGE IN THE NEWBORN INFANT.: An Evaluation of Two Methods

ABSTRACT. Vogt, H., Haneberg, B., Finne, P. H. and Stensberg, A. (Department of Paediatrics, University of Bergen, and Department of Clinical Chemistry, Akershus Central Hospital, University of Oslo, Norway). Clinical assessment of gestational age in the newborn infant. An evaluation of two methods. Acta Paediatr Scand, 70:669,.–The scoring systems of Dubowitz et al. and Parkin et al. were evaluated in two selected materials of newborn infants referred to a neonatal unit. Our estimation of gestational age by Dubowitz scores tended to be too high for the extreme prematures. “Small‐for‐dates” were also overestimated, whilst “appropriate‐for‐dates” and infants with respiratory difficulties were underestimated. “Large‐for‐dates” fell close to the standard curve. Ninety‐five per cent confidence limits were up to ±5 weeks for Dubowitz scores and nearly ±6 weeks for Parkin scores. Further statistical analysis displayed some limitations in the use of linear regression formulas for scoring systems based on external and/or neurological characteristics. Thus, the results obtained with these methods must be used with caution in some selected newborn materials.

Systemic and mucosal antibody responses to group B streptococci following immunization of the colonic-rectal mucosa

The cervico-vaginal mucosa is poorly designed for inducing a mucosal immune response, but it can effect such a response evoked at other mucosal sites. This study was undertaken to determine whether colonic-rectal immunization with group B streptococci (GBS) might induce a local cervico-vaginal immune response. Mice were immunized with either fragmented GBS rectally, whole GBS rectally, or whole GBS subcutaneously. Cholera toxin (CT) was used as an adjuvant for the rectal immunizations. Following colonic-rectal immunization with whole GBS, the mean anti-GBS IgA antibody level in vaginal secretions was 735 kU/ml, with individual values reaching 3480 kU/ml. Corresponding levels of IgA antibodies never exceeded 10 kU/ml in serum and intestinal secretions, or 90 kU/g in feces. In vaginal secretions IgA antibodies to GBS also constituted a much larger fraction of total IgA than in serum, intestinal secretions and feces. Immunizations with fragmented GBS produced much lower IgA responses. Anti-GBS IgA response at the inductive site in the colon-rectum was not significant, as opposed to a strong anti-CT IgA response. Except in serum, the anti-GBS IgG responses to colonic-rectal immunizations were generally low, or absent. The results may provide a basis for the development of mucosal vaccines against GBS-infection.

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 Crohns 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)

ACUTE HEMOLYTIC ANEMIA RELATED TO DIPHTHERIA‐PERTUSSIS‐TETANUS VACCINATION

ABSTRACT. Three infants developed severe hemolytic anemia following the second or third diphtheria‐pertussistetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis. The presence of IgM on the erythrocytes from 2 of the infants could be demonstrated by antiglobulin tests or immunization experiments. Heat eluates of the erythrocytes from one of the infants contained antibodies to tetanus and diphtheria toxoids, as well as to Bordetella pertussis, suggesting that these antibodies were antigenically bound to the erythrocytes. Virus antibodies or isoagglutinins, present in the serum, were not found in the eluate. No antibodies against the vaccine components could be demonstrated in eluates of erythrocytes from control subjects. In vitro experiments showed that tetanus and diphtheria toxoids were easily bound to human erythrocytes. This finding could help explain the pathogenesis of the autohemolysis.

LYSOZYMES IN FECES FROM INFANTS AND CHILDREN

ABSTRACT. Haneberg, B. and Finne, P. (Department of Pediatrics and the Broegelmann Research Laboratory for Microbiology, The University of Bergen, School of Medicine, Bergen, Norway). Lysozymes in feces from infants and children. Acta Paediatr Scand, 63: 588, 1974.—An agar diffusion technique seemed useful for the assay of lysozyme activity in serum, milk, and extracts of freeze‐dried feces. Normal levels of this activity were established before the method was applied to extracts of feces from premature infants, receiving either human milk, with lysoyme activity of its own, or cows milk with or without added albumen lysozyme. Results of these investigations, in addition to immunologic studies, using antisera to human and albumen lysozymes, indicated that human milk lysozyme and albumen lysozyme in cows milk formula may pass through the infants intestinal tract. Albumen lysozyme, however, will most often be inactivated before being excreted with feces. Low fecal pH was found in those receiving albumen lysozyme as well as in those receiving human lysozyme. This may reflect the intestinal activity of the lysozymes. Low intestinal pH, brought about by lactulose in the cows milk feed, did not in itself lead to increased lysozyme activity. At present, no advantage of adding albumen lysozyme to cows milk formula has been substantiated.