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Biomedical subjects

L Mellander

Publications and source records attributed to L Mellander.

At least 19 recordsLinked to original sources

A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life.

In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.

Age Factors

Presence of non-maternal antibodies in newborns of mothers with antibody deficiencies.

To explain the mechanism for induction and production of specific antibodies found in the newborn already at birth, without previous known exposure to the antigen, we chose a model that presumably excluded the possibility of specific antibodies being transferred from the mother to the fetus. Specific IgG, IgA, and IgM antibodies against Escherichia coli and poliovirus antigens were determined with ELISA in serum, saliva, and amniotic fluid from hypogammaglobulinemic and IgA-deficient mothers as well as in cord serum, saliva, and meconium from their offspring. All the mothers lacked IgA and some also lacked IgM antibodies, which were found in their healthy newborns. The amniotic fluid from a hypogammaglobulinemic mother lacking IgA contained small amounts of IgA antibodies, which were also found in the neonate, suggesting a fetal origin. There was evidence for the presence of antiidiotypic antibodies to poliovirus in the cord sera. We propose that idiotypic and/or antiidiotypic IgG antibodies transferred via the placenta from the mother to the fetus can initiate specific immune responses seen in the newborn. Thus, it may be that transplacental IgG not only passively protects the newborn, but also actively primes the fetus during fetal life via its content of idiotypic and/or antiidiotypic antibodies.

Agammaglobulinemia

Interaction of P-fimbriated Escherichia coli with human meconium.

The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.

Adhesins, Escherichia coli

Longitudinal growth in children with non-Hodgkin's lymphoma and children with acute lymphoblastic leukemia: comparison between unirradiated and irradiated patients.

Longitudinal growth was studied in children treated for non-Hodgkin's lymphoma (NHL). The aim of the study was to compare these children's growth velocity with findings in a previous study we performed on age-matched children with acute lymphoblastic leukemia (ALL) who received cranial irradiation. Nine children with NHL with an onset time of treatment between 4 and 9 years of age (mean 6.5 years) were studied with annual body measurements taken from the time of the diagnosis and thereafter annually during the following 4 years. None of the children received cranial irradiation. During the first treatment year a significantly low mean height velocity was observed (-1.4 standard deviation score [SDS]) for the NHL group. The consecutive two 1 year periods showed a normalization of the mean height velocity. For the group of children with ALL, there was a more prominent negative effect on height during the first 2 years of treatment than for the NHL group in the present study. After the cessation of therapy, the children with NHL showed a reduced catch-up growth compared with the children with ALL. The explanation offered is that cranial irradiation has a heavier impact on growth than chemotherapy during the first 2 years of treatment, but an intense chemotherapy during the maintenance period could have a considerable impact in blunting growth.

Antineoplastic Combined Chemotherapy Protocols

A longitudinal study of growth and growth hormone secretion in children during treatment for acute lymphoblastic leukemia.

Diminished growth rate during treatment for acute lymphoblastic leukemia (ALL) is of the multifactorial etiology. Effects on GH secretion have been shown after discontinuation of treatment including prophylactic CNS irradiation. Seventeen children treated for ALL with three different CNS preventive schedules were followed longitudinally with repeated estimations of the spontaneous GH secretion during a 24-month period. No difference was found in GH secretion during this time between patients who had received no radiotherapy and those who had received 18 or 24 Gy as CNS prophylaxis. During dexamethasone treatment the GH secretion was completely suppressed, which can be a mediator for the diminished growth rate during the first 2 years of ALL treatment. We conclude that there is no clinical reason to perform GH analysis within the first 24 months of treatment for ALL.

Antineoplastic Combined Chemotherapy Protocols

Comparison of serum and salivary antibodies in children vaccinated with oral live or parenteral inactivated poliovirus vaccines of different antigen concentrations.

A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).

Antibodies, Viral

Specific antibodies to poliovirus type I in breastmilk of unvaccinated mothers before and seven years after start of community-wide vaccination of their infants with live, oral poliovirus vaccine.

Secretory IgA (SIgA) antibodies against poliovirus type 1 were determined using the ELISA method in breastmilk samples obtained each month from 100 young, healthy, unvaccinated mothers living in urban slum areas of Lahore, Pakistan. The study covered two different groups, one in 1980-1981 and the other in 1987, before and seven years after a nation-wide expanded programme of childhood immunization (EPI) had started. The SIgA titres did not change neither with duration of lactation nor with time after vaccination in the infants of the mothers studied. The seasonal breastmilk IgA antibody titres to poliovirus type 1 corresponded to the epidemiological conditions existing both before (1980-81) and after general vaccination coverage with live, oral poliovirus vaccine (OPV) had reached 80% of the infant population (1987). Neutralization titres did not seem to correlate well with ELISA titres although colostrum samples had high levels of neutralizing antibodies. The wide variation between high (greater than 10,000) and low (less than 500) individual breastmilk IgA antibody titres observed during various seasons could be of consequence for the breast-fed baby. Colostrum, which was also found to have significant neutralization capacity, might interfere with the OPV now often given on the day of birth.

Adult

The antibody response in breast-fed and non-breast-fed infants after artificial colonization of the intestine with Escherichia coli O83.

The local and systemic antibody response after oral administration of a nonenteropathogenic type 1 fimbriated Escherichia coli O83 strain was followed in nine breast-fed and eight formula-fed infants during their first 15 wk of life. Five breast-fed and six formula-fed infants were followed as controls. E. coli O83 was detected in the stools of colonized infants from d 2 after colonization and persisted in the intestine for up to 26 wk. The percentage of children successfully colonized with E. coli O83 was higher among breast-fed than among formula-fed colonized infants. Also, the O83 bacteria isolated from the breast-fed children had a higher capacity to attach to colonic epithelial cells of the HT-29 cell line than those isolated from bottle-fed infants. E. coli O83 IgA and IgM antibodies estimated by ELISA were significantly elevated in the saliva of colonized as compared with control infants 2-7 wk after colonization. IgA antibodies against O83 were also higher in the stool of colonized formula-fed infants than in formula-fed controls. The results suggest that the mucosal immune system of the newborn infant can be triggered early to produce specific antibodies against bacteria colonizing the intestine.

Antibodies, Bacterial

The influence on the secretory IgA antibody levels in lactating women of oral typhoid and parenteral cholera vaccines given alone or in combination.

41 lactating Pakistani women were vaccinated orally with Salmonella typhi vaccine alone or in combination with parenteral Vibrio cholerae whole cell vaccine, in order to study the possible difference in the secretory response after live and inactivated vaccines. The antibody response in saliva, milk and serum was recorded using the enzyme-linked immunosorbent assay, ELISA. All had prevaccination antibody levels against the 2 vaccines. The live S. typhi vaccine gave a serum IgG and IgA response but did not influence the IgM levels. Salivary or milk secretory IgA (SIgA) antibody levels showed both increases and decreases but in most cases remained unchanged. Even if the vaccine was given in enteric coated capsules, the milk and salivary SIgA response was more often decreased than increased, although somewhat higher serum IgG levels were attained with this preparation. Parenteral cholera vaccination enhanced both serum and SIgA milk antibody response. Combination of the 2 vaccines did not have any untoward effect on the antibody response in serum or in secretions against V. cholerae or S. typhi LPS. The results show that an oral vaccine often induces a rather poor, or even negative mucosal antibody response, while a parenteral vaccine provokes a substantial SIgA response in individuals orally primed by natural exposure. This is in agreement with our previous findings with oral and parenteral poliovirus vaccines in this population.

Administration, Oral

Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged.

A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 in order to cease an outbreak of poliomyelitis. We followed eight IgA-deficient individuals and nine controls for poliovirus excretion in feces and for antibody responses in serum and saliva. Five weeks after oral poliovirus vaccination all eight IgA-deficient individuals were still excreting polioviruses, in contrast to one of nine controls. The concentration of polioviruses, as estimated by a semi-quantitative immunofluorescent assay, was generally higher and the test was significantly more often positive in the samples from the IgA-deficient individuals. Although serum levels of antibodies to poliovirus type 3 were lower in IgA-deficient individuals before vaccination, both measurements showed that the two groups had similar antibody levels 4 weeks after vaccination. IgA-deficient individuals lacked salivary IgA antibodies to poliovirus types 1 and 3 but had increased levels of IgM antipolio antibodies, which were shown to carry secretory component. We conclude that the mucosal IgM antibodies of IgA-deficient individuals eliminate polioviruses less efficiently than do the IgA antibodies of normal individuals.

Adolescent

Growth in children treated for acute lymphoblastic leukemia with and without prophylactic cranial irradiation.

Growth and weight gain were studied longitudinally over a period of four years in thirty-nine children treated for acute lymphoblastic leukemia. The children were divided into two groups according to treatment. Twenty-eight children were given prophylactic cranial irradiation and eleven children were treated without such irradiation. The duration of cytostatic treatment was three years in all cases. Average growth during the first two years was similar in the two groups, and the standard deviation scores (SDS) were below average. The rate of growth (in height) during the fourth year was significantly higher among those children who had not received cranial irradiation (p less than 0.01). After four years the average attained height had declined 0.5 SD for children treated with cranial irradiation and 0.2 SD for children without such treatment. Weight velocity was significantly greater than the expected mean in the non-irradiated group during the first year and in the irradiated group during the fourth year of the study. Attained weight after four years had increased 0.4 SD more among those children who had not received irradiation. The results suggest that prophylactic cranial irradiation is responsible for the greater part of the prepubertal growth inhibition in these children.

Child

Growth hormone secretion and response to growth hormone therapy after treatment for brain tumour.

Children irradiated for brain tumours constitute an increasing group of patients who will require GH therapy. High-dose cranial irradiation is necessary for cure, but inevitably causes GH deficiency within a few years. In 19 patients investigated between 2 and 9 years after irradiation, the spontaneous 24-hour GH secretion was markedly reduced. The secretory pattern indicated loss of regulating hypothalamic hormones. After exogenous GHRH was administered, the pituitary was able to respond with a prompt GH release, showing that pituitary function was unaffected. Ten prepubertal children growing at 3.8 +/- 0.3 cm/year were treated with GH, 0.1 IU/kg/day s.c. Their growth rate increased to 8.2 +/- 0.4 cm in the first year. An increased growth rate was also maintained in the second year.

Adolescent

Echocardiographic findings in children treated for malignancy with chemotherapy including adriamycin.

Thirty-seven children receiving chemotherapy including adriamycin were studied with echocardiography. Abnormal left ventricular function assessed by systolic time intervals (STI) and/or left ventricular shortening fraction (delta LVID) was present in 30%, and dilated left ventricle was in 45% of the case, often accompanied by thinning the left ventricular wall. Three patients developed congestive heart failure, one with fatal outcome. Two of these patients had received chest irradiation along with the chemotherapeutic treatment. These three patients with overt heart failure had gross abnormalities in several echocardiographic variables of which delta LVID seemed most specific.

Adolescent

Anthropometry and subsequent mortality in groups of children aged 6-59 months in Guinea-Bissau.

To assess the importance of nutritional status for subsequent survival, 2228 children aged 6-59 mo were followed for 8-12 mo in four different areas of Guinea-Bissau. The overall death rate was 0.62/100 child-months of follow-up (126 deaths) and 0.63 for the 1756 children who were examined on entering the study (109 deaths). Mortality was twice as high in the periurban as in the rural areas due to an outbreak of measles. In a bivariate analysis the relationship between nutritional status indicators and mortality was confounded by the age dependence of both. Using Cox's regression technique, height-for-age but not weight-for-height was positively correlated with survival. The number of children in the household was a better discriminator for death from measles than was nutritional status. Long-term factors, probably of multiple social origin, are likely causes of both relatively short stature and high mortality.

Body Height

A longitudinal study on growth and spontaneous growth hormone (GH) secretion in children with irradiated brain tumors.

Longitudinal growth was studied in 27 children after radiotherapy for a brain tumor. Growth deviation (greater than or equal to 1 SD) was found in 56% of the children after 2 years and was most profound in prepubertal children aged between 3 and 8 years at the time of irradiation. In this group growth velocity was markedly reduced and no catch up was seen. In all children studied growth hormone (GH) secretion, measured as the spontaneous secretion over 24 hours, was found to be severely disturbed. Our conclusion is that all children with a growth deviation greater than or equal to 1 SD after radiotherapy (greater than or equal to 40 Gy) to the hypothalamo-hypophyseal region should be considered GH deficient. In such children GH treatment can be initiated without further testing.

Adolescent