Anja Tiilikainen

Changing pattern of cow's milk intolerance. An analysis of the occurrence and clinical course in the 60s and mid-70s.

ABSTRACT. Verkasalo, M., Kuitunen, P., Savilahti, E. and Tiilikainen, A. (Childrens Hospital, University of Helsinki, Finland). Changing pattern of cows milk intolerance. Acta Paediatr Scand, 70: 289, 1981.–The rapid changeover to commercial adapted infant formulae which took place in Finland between 1973 and 1975 was studied as a factor in the occurrence of severe intestinal cows milk intolerance (CMI). Of infants treated for CMI in 1962‐73, ninety‐three percent (25/27) were on homemade or unadapted formulae. The admission rate for CMI in these years was 0.22/1 000 liveborn infants breast fed less than six months. During 1974‐77 the corresponding figure was 0.56, with 85 % of the patients (18/26) on adapted cows milk formulae. The patients treated before 1974 had a longer symptomatic period before admission, greater growth retardation and more severe intestinal damage than those seen during and after 1974. This is believed to reflect mainly the increasing awareness of CMI on the part of both laymen and the medical profession. In the history of 2/3 of the patients at least one of the following conditions was noted: non‐breast feeding, infectious gastroenteritis, praematurity, 21‐trisomy, prior intra‐abdominal surgery, Hirschsprungs disease, and atopic disease in family members. The long follow‐up averaging over four years revealed four patients with coeliac disease. In one of these the proximal jejunal mucosa was normal after two years on gluten‐containing diet, but he showed a mucosal relapse as late as between 2 to 4 years on normal diet.

Genetic Background of Acute Anterior Uveitis

To determine the hereditary pattern of acute anterior uveitis, we examined seven families-one family with four cases, one family with three cases, and four families with two cases of acute anterior uveitis. A total of 16 patients with uveitis and 28 relatives underwent ocular examinations and serologic determination of HLA antigens, protease inhibitor alpha 1-antitrypsin typing, and X-ray examination of sacroiliac joints. Sacroiliitis was found in 11 of 16 patients (68.8%) and incomplete Reiters disease in seven of 16 (43.8%). HLA-B27 antigen was found in all patients with uveitis and in six of 21 (28.6%) relatives. HLA-Cw1 antigen was found in nine of 14 (64.3%) patients with uveitis, often in the same haplotype with HLA-B27 antigen. HLA-DR4 antigen was found in seven of 11 (63.6%) patients with uveitis. There was no significant association of the alpha 1-antitrypsin variant MZ with uveitis. We believe that a pleiotropic gene associated with HLA-B27 antigen with autosomal dominant inheritance, incomplete penetrance, and variable expressivity may determine susceptibility to acute anterior uveitis in linkage disequilibrium with HLA-Cwl antigen.

HLA-compatible donor cornea for prevention of allograft reaction

Our series comprises 80 penetrating grafts. Of the recipient corneas 36 were vascularized. Of the donor corneas 48 were fresh and 32 were cryopreserved. As prophylaxis, we gave topical and systemic prednisolone, combined, in heavily vascularized cases, with azathioprine. Corneal donor-recipient pairs were divided into three groups according to HLA histocompatibility. In Group I (0–1 mismatch) the rate of allograft reaction was 1 in 27, in Group II (2–4 mismatches) it was 4 in 19, and in the untyped Group III 9 in 34. Even when the prognosis was poor, a well-matched donor cornea (Group I) greatly improved the chances of success; when the corneal bed was vascularized, the well-matched donor corneas had a failure rate of 1 in 13, whereas in untyped pairs it was 7 in 18. The importance of possible presensitization is discussed. Das Untersuchungsmaterial umfaßt 80 Augen nach penetrierender Keratoplastik. In 36 Fällen fand sich die Empfängerhornhaut vaskularisiert und in 44 avaskulär. 48 der Spenderhornhäute waren frisch und 32 eingefroren. Prophylaktisch wurde Prednisolon lokal und systematisch kombiniert mit azathioprine in stark vaskularisierten Fällen verabreicht. Die Spender-Empfänger-Paare wurden gemäß ihrer Histokompatibilität in drei Gruppen eingeteilt. Bei bester Übereinstimmung war das Verhältnis der Allograftreaktion 1 zu 27, in Gruppe II mit 2–4 fremden Antigenen war sie 4 zu 19 und in Gruppe III ohne Bestimmung der HLA-Antigene war sie 9 zu 34. Spenderhornhaut mit guter Übereinstimmung, d.h. 0–1 fremdem Antigen scheint recht zuverlässig auch in Fällen mit schlechter Prognose. In vaskularisierter Empfänger-Hornhaut und Spender mit guter Übereinstimmung war das Verhältnis der mißlungenen Transplantationen 1 zu 13 und bei nicht typisierten Paaren 7 zu 18. Die Rolle einer Präsensibilisierung wird diskutiert.

Early fusion of two human embryos

An infant chimaera with an XX and an XY cell line is described. She had a macroscopically and histologically normal ovary on the right and an ovotestis on the left. Biopsies from the gonads revealed 1–15% of XY cells as judged by fluorescent Y body findings of uncultured cells as well as by karyotypes of mitoses from long term cultures. Ovarian and testicular structures had similar frequencies of the two cell lines. There was no evidence of in vitro selection of cells during tissue culture.

HLA ANTIGENS IN INTESTINAL COW'S MILK ALLERGY

ABSTRACT. The histocompatibility antigens of one hundred patients with a severe form of cows milk allergy were studied. HLA‐A and B locus antigens were identified in all patients, C locus antigens in 62 patients and DR locus antigens in 41 patients. The A, B and C locus antigen frequencies were compared with those of healthy blood donors, and DR locus antigen frequencies with those of healthy unrelated volunteers and cadaver kidney donors. The series included six patients with concomitant coeliac disease, who were treated as a separate group. No statistically significant differences between the patients and controls were observed, but suggestive differences became apparent when the patient group was divided into subgroups according to the presence or absence of certain co‐existing conditions, and the severity of the initially observed intestinal lesion. It is concluded that several factors contribute to the pathogenesis of intestinal cows milk allergy, and that in some cases genes linked to the HLA region may play a role.

The separation of genetically different lymphocyte populations in vitro.

SUMMARY A method of separating two mixed antigenically heterogeneous human lymphocyte populations is presented. The technique is based on the observation that the nonspecific proteolytic enzymes pronase and nagarse dissolved the cell wall of nonviable cells treated with specific cytotoxic human antiserum and rabbit complement, while similarly treated nonantigenic cells remained undamaged. A 1% minority population of antigenically different cells could be distinguished by this method. Possible applications of the method are discussed.

HLA‐B 12 AND HLA‐B 27 ANTIGENS AND SUSCEPTIBILITY TO THE CORNEAL ALLOGRAFT REACTION

Our series comprised 100 penetrating corneal transplantations: 36 cases with HLA‐B 12 and/or B 27 antigen in the recipient and, as controls, 64 cases without these antigens. The cornea was vascular in 44% of the HLA‐B 12/B 27 group and in 40% of the controls.

Immunological and genetic markers in a family with Hashimoto's disease.

A family with Hashimotos disease in three generations is described. Seven persons (all female) had Hashimotos disease and four of them were initially hypothyroid. Hashimotos disease was the only thyroid disorder occurring in this family; no other autoimmune disease was observed. Circulating thyroid antibodies were detected in all seven subjects with overt thyroiditis in this family. Thyroid antibodies were also detected in low titres in about half of the healthy relatives. Evidence of thyroid antigen‐directed cell‐mediated immunity was demonstrated using the leucocyte migration inhibition test in four out of seven subjects with thyroiditis and also in about half of the relatives without clinical thyroid disease. The relative number of thyroglobulin‐binding circulating lymphocytes was elevated in six subjects with Hashimotos disease. Again, the percentage of such cells was also increased in about half of the‘healthy’relatives. Thyroid‐stimulating immunoglobulins were detected by the radio receptor assay in three of the seven subjects with Hashimotos disease and in four out of thirteen relatives without overt signs of thyroiditis. In conclusion, all subjects with Hashimotos disease carried immunological markers of autoimmune thyroid disease in the circulation. In addition, most of the‘healthy’relatives were also positive for some or all of the markers sought in this study. The expression of these markers thus seems to be variable. No clear‐cut conclusion could be drawn regarding the inheritance of these markers. H LA genotypes were assayed for thirty‐five specificities of A, B and C loci and five of the D loci. There was no correlation between any individual antigen or HLA haplotype and overt Hashimotos disease in this family.

FOETOMATERNAL HISTOINCOMPATIBILITY IN TOXAEMIA OF PREGNANCY

SUMMARY Lymphocytotoxic antibodies were more frequent (by micro cytotoxicity assay) in the Primigravidae suffering from toxaemia in pregnancy than in normal Primigravidae, but in multigravidae the respective antibody frequencies were of the same magnitude. In mixed leukocyte cultures, maternal lymphocytes developed a faster or stronger response to stimulating cells from the children born after a toxaemic pregnancy, than to cells from other siblings who had inherited the same paternal HL-A haplotype. Foetomaternal incompatibilities in non HL-A leukocyte antigens, ABO antigens or Gm and Inv factors did not satisfactorily explain the difference. Immunofluorescence staining of toxaemic kidney biopsies revealed glomerular aggregates specifically binding fluorescein-conjugated rabbit anti-human IgG + IgM antibody.