M. Gahr

Sequential determination of CRP, α1-antitrypsin and haptoglobin in neonatal septicaemia

ABSTRACT. In 312 preterm and term newborn infants serum concentrations of C‐reactive protein (CRP), haptoglobin and α1‐antitrypsin were measured during several days by radial immunodiffusion. In addition white blood cell count and the ratio of band to total neutrophils (B/N‐ratio) were determined. In 12 infants with proven sepsis CRP was found elevated above the upper limit of the normal range (20 mg/l). Successful therapy was followed by a decrease of CRP concentration. In infants with suspected infection high CRP values were found in most cases. In contrast, haptoglobin and α1‐antitrypsin concentrations differed not significantly between the group of infants without infection, with proven and with suspected infection. White blood cell count and B/N‐ratio also were not appropriate for the early identification of bacterial infection in the newborn period.

Generalised glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with diminished specific activity (GPI Homburg)

A new glucosephosphate isomerase (GPI) variant is described which is characterised by very low specific activity in erythrocytes, granulocytes and muscle tissue, nearly normal stability, normal kinetic properties and a decreased electrophoretic mobility. The propositus suffers from a complex syndrome involving erythrocytes (congenital haemolytic anaemia), granulocytes (decreased production of superoxide anion and reduced bactericidal activity in vitro) and the neuromuscular system (myopathy, mental retardation). It is suggested that the clinical syndrome results from generalised GPI deficiency due to a decreased specific activity of the variant enzyme, which cannot be compensated by an increase of de-novo synthesis of GPI protein even in cells exhibiting active protein synthesis such as granulocytes and muscle cells.

Triosephosphate isomerase deficiency: haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity.

A new triosephosphate isomerase (TPI) variant is described in an 8-year-old Turkish girl suffering from chronic haemolytic anaemia, myopathy and developmental retardation since early infancy. The enzyme activity profile revealed a generalized deficiency in erythrocytes, granulocytes, mononuclear blood cells, skeletal muscle tissue and cerebrospinal fluid. The concentration of enzyme substrate dihydroxyacetone phosphate was distinctly elevated. Biochemical examination showed accelerated enzyme deamidation, the first step in the normal catabolism of TPI during aging of the erythrocyte. The specific activity of the variant TPI, determined by antibody titration, was reduced to 61% of normal. Its heat stability was markedly decreased. Muscle biopsy and neuropsychological testing further clarified the pathogenesis of the disorder. A prevalent alteration of mitochondria similar to that seen in mitochondrial myopathy and an elevated amount of intracellular glycogen were found. The patients retarded intellectual development was mainly due to impaired visual perception and sensory-motor co-ordination in addition to a lack of syllogistic reasoning. The findings indicate that the low TPI activity leads to a metabolic block of the glycolytic pathway and hence to a generalized impairment of cellular energy supply.

Immunologic evaluation of children with homozygous beta-thalassemia treated with desferrioxamine

In 15 children with thalassemia major (age 4-17 years) a detailed analysis of different immune functions was performed: phagocyte function, specific cellular immunity, humoral defense system. All patients had been subjected to a desferrioxamine therapy and a high transfusion regimen. Examination of neutrophil function included adherence, random migration, chemotaxis, killing of Escherichi coli and production of superoxide radical; these neutrophil functions were shown to be normal. In addition, lymphocyte proliferation in response to different lectins (phytohemagglutinin, concanavalin A, pokeweed mitogen) was identical in patients and controls. However, the number of circulating T-lymphocytes, helper T-cells and B-lymphocytes was increased in some patients. This phenomenon probably reflects an unspecific stimulation of the antibody-producing cells by repeated blood transfusions.

Phagocytic activities in neonatal monocytes

Monocytes play an essential role in cellular host defense as circulating phagocytes, as well as precursors of macrophages. We investigated the principal phagocytic activities in monocytes from cord blood of term infants by analysing adherence, random migration, chemotaxis, bactericidal activity, phagocytosis-associated chemiluminescence, production of superoxide anion (O2−) and generation of hydrogen peroxide (H2O2). All phagocytic functions of monocytes from neonates were shown quantitatively to be comparable to those of cells from healthy adult volunteers. The increased susceptibility of the human neonate to serious systemic infections cannot be related to an abnormality in monocyte function.

Pneumatosis intestinalis in children with leukaemia: Report of three cases

Three children with leukaemia (one with acute myeloid, two with acute lymphoblastic leukaemia) developed pneumatosis intestinalis during cytostatic treatment. The aetiology of pneumatosis intestinalis in these children could not be elucidated. Pneumatosis intestinalis may be caused by entry of gas into a bowel wall which is altered by steroid or cytostatic treatment. Otherwise, anaerobic bacteria may produce gas in the intestinal walls, therefore we treated all children with metronidazol.

A new defect of neutrophil chemotaxis and random motility in a child with recurrent bacterial infections and hyperimmunoglobulinemia E.

A new defect of chemotaxis and random motility of polymorphonuclear leukocytes is described in a patient with severe recurrent bacterial infections since early childhood. This defect seems to be intrinsic to the cells. The patients plasma did not contain an inhibitor of chemotaxis. Addition of plasma to the patients cells restored their chemotactic activity. High concentrations of immunoglobulin E were found in the patients plasma.Phagocytosis, bacterial killing, and reduction of nitroblue tetrazolium salt were normal. Histological examination of lung tissue revealed a pattern similar to that observed in chronic granulomatous disease.

The γ-chain heterogeneity of haemoglobin F in German infants

Abstractγ-chain heterogeneity of haemoglobin F was studied in German full-term and preterm infants up to 12 months old. The AγT-gene frequency calculated was about 19%. In most cases with AγI-/AγT-chain heterogeneity AγI-chains predominated over AγT-chains. There was no difference between infants with or without the AγT-chain concerning haemoglobin F-concentration, F-cell percentage or Gγ-chain percentage. The Gγ-chains accounted for 69.2%±3.3% (SD) of the total γ-chains in full-term newborn infants with a decrease to 42.5%±6.5% during the first 6 months. Comparison of the Gγ-chain decrease in preterm and in full-term newborn infants suggests a more pronounced decrease during extrauterine life than during the intrauterine course.

ELASTASE-|[alpha]|1-PROTEINASE INHIBITOR IN NEONATAL SEPTICEMIA AND HYALINE MEMBRANE DISEASE

Elastase, a neutral protease stored in the azurophillic granules of neutrophils, is immediately released during the process of phagocytosis and rapidly bound and inactivated by α1-proteinase inhibitor. This complex (E-α1-PI) is of high stability and can be identified by an ELISA-assay. In our study 95 % of all infants with neonatal septicemia and/or meningitis had significantly increased plasma levels of E-α1-PI at time of diagnosis (n=37). Only two patients with group B streptococcal septicemia (GBS) were missed initially, both of them displayed marked leukopenia and neutropenia at time of diagnosis. Nevertheless determination of E-α1-PI was helpful in distinguishing patients with early onset streptococcal disease (n=13) from those with hyaline membrane disease (HMD; n=30). 85 % of the neonates with GBS had increased plasma concentrations of E-α1-PI at age of diagnosis. In contrast all patients with HMD had E-α1-PI levels within the normal range. After initiation of therapy normalization of E-α1-PI levels was observed in all neonates who recovered from infection. These data suggest that E-α1-PI is a sensitive and rapidly responsive indicator of neonatal septicemia. In addition E-α1-PI may be helpful in monitoring the course of the disease.

CHRONIC GRANULOMATOUS DISEASE (CGD): ISOLATED DEFECT OF THE NADPH-OXIDASE ACTIVITY IN NEUTROPHILS

CGD is characterized by deficient membrane bound NADPH-oxidase activity in phagocytes. These patients suffer from severe recurrent bacterial and fungal infections. In a boy with typical clinical history of CGD, investigations of his total leukocytes showed reduced cytochemical nitrobluetetrazolium (NBT)-reduction (30-48 % NBT-positive phagocytes), decreased O2−-production in response to the phorbolester PMA and low glucose oxidation. Because in typical CGD-patients at least 99 % of the phagocytes are NBT-negative, we suspected a variant of CGD. Extensive examinations in pure (> 98 %) preparations of polymorphonuclear leukocytes (PMN) gave results compatible with classical CGD: absent production of chemiluminescence and oxygen metabolites (O2−, H2O2) after stimulation with PMA and opsonized zymosan, low glucose oxidation, decreased bactericidal capacity and 99 % NBT-negative PMN. However, in monocytes of the patient, a nearly normal PMA-induced O2−-formation has been found (11.4 nmole O2−/h/2×105 cells, controls 18.2±2.3). The same was true with H2O2-production. In addition the patients macrophages, cultivated in a long term culture, similarly released oxygen metabolites after stimulation of the respiratory burst with either PMA of opsonized zymosan. We demonstrate here an isolated defect of the NADPH-oxidase activity in neutrophils of a patient with CGD.