Antonella Sciotto

Glucose-6-phosphate dehydrogenase deficiency in Sicily. Incidence, biochemical characteristics and clinical implications.

This report deals with the incidence, type and clinical implications of G6PD deficiency in Sicily. Of 3347 male subjects examined, 56 were deficient in G6PD. They were distributed throughout the island. The G6PD levels in RBC were almost zero; in leukocytes, platelets and saliva they were found to be 26%, 18% and 16%, respectively, of controls. The Michaelis constant for NADP and G6PD was lower than for controls. Conversely, the utilization of the analogous Gal6P and 2dG6P was higher. The thermostability of the enzyme was lower and the pH optima (6.5 and 9.5) were different from the controls. An identical electrophoretic pattern was found both in normal and deficient subjects. This pattern is superimposable on that described as Mediterranean variant. The analysis among 270 subjects admitted to our Clinic with hemolysis due to G6PD deficiency demonstrated that the most frequent disease is favism, followed by neonatal jaundice, while hemolysis due to drugs is very rare. Ingestion of fresh fava beans was the most frequent cause of favism, but cases occurred after breast feeding and inhalation of pollen.

Effect of Alpha-interferon on Natural Killer Cell Activity and Lymphocyte Subsets in Thalassemia Patients with Chronic Hepatitis C

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.

Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura

Abstract: Interleukin‐6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute‐phase response. IL‐6 is also an important thrombocytopoietic factor. High serum levels of IL‐6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin‐like function of IL‐6, we measured IL‐6 levels in the serum of patients affected by post‐infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL‐6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL‐6 in acute thrombocytopenic purpura and, very probably, IL‐6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL‐6 is another acute‐phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms.

INSULIN AND GROWTH HORMONE SECRETION IN A LEUKAEMIC GIRL WITH HYPOTHALAMIC SYNDROME

Abstract Schilirò, G., Russo, A., Sciotto, A. and Vigo, R. (Paediatric Clinics I and II, University of Catania, Catania, Italy). Insulin and growth hormone secretion in a leukaemic girl with hypothalamic syndrome. Acta Paediatr Scand, 66:261, 1977.—The authors report a girl with acute lymphoblastic leukaemia presenting hypothalamic syndrome characterized by meningeal leukaemia, hyperphagia and obesity. Insulin and growth hormone secretion, studied with arginine and insulin stimulation tests, showed a high peak of serum insulin and no response of growth hormone. Insulin and growth hormone responses to these tests reverted to normal after intrathecal methotrexate.

Leg ulcer in a patient with agammaglobulinaemia.

A 12-year-old boy with a large ulcer on the right leg was admitted to our department. The cutaneous ulcer had been unsuccessfully treated for about 6 months with various systemic antibiotics, topical medications, and finally skin graft. His medical history revealed an episode of meningoencephalitis at the age of 6 years. Although he had been diagnosed, on that occasion, with agammaglobulinaemia, he had never received immunoglobulin replacement. On admission, culture of the skin lesion yielded Staphylococcus aureus. Serum concentrations of all classes of immunoglobulin were severely decreased, with IgM being undetectable; peripheral B cells were absent. These laboratory findings are diagnostic for Bruton agammaglobulinaemia. After the first intravenous immunoglobulin administration, the culture became negative and a striking improvement of the ulcer was noticed. Continuous immunoglobulin replacement, every 3 weeks, resulted in complete healing of the leg ulcer in 2 months. After 18 months follow-up, the patient is still on intravenous immunoglobulin administration and is well and free of infections.

Immunological changes in β-thalassemia major patients positive for HTLV-III antibodies

Antibodies to HTLV-III were found in 6 of 206 Sicilian patients with thalassemia major, aged 1 to 30 years. None of the patients showed clinical signs related to immuno-deficiency syndromes. Immunological investigations carried out in all positive patients showed alterations similar to those found in thalassemic patients without antibodies to HTLV-III. These immunological changes could not depend on the HTLV-III infection, but could be related to the thalassemic condition.

Lymphocyte Changes in Favism: in vitro Evidence of a Modifying Effect of Bilirubin and Hemoglobin on T-Lymphocyte Receptors

Lymphocyte subpopulations were studied in 13 Sicilian glucose-6-phosphate dehydrogenase (G6PD)-deficient children during and after the hemolytic crisis due to fava bean ingestion. A statistically significant reduction of sheep-red-cell (SRC)-rosetting lymphocytes occurred in all patients during the hemolytic crisis, whereas B lymphocytes were not affected. In order to establish the possible relationship between serum changes occurring during hemolysis and reduction of SRC-rosetting lymphocytes, the effect in vitro of varying concentrations of bilirubin and hemoglobin on the rosette formation capacity of lymphocytes was studied. Both substances produced a statistically significant reduction of SRC-rosetting lymphocytes both in normal and deficient subjects. This effect showed a direct relationship with the concentrations of bilirubin and hemoglobin used and was more pronounced on lymphocytes from G6PD-deficient children. These data suggested that the reduction of SRC-rosetting lymphocytes observed during acute hemolysis of favism can be related to a modifying effect of bilirubin and hemoglobin.

Transient increase of fetal haemoglobin in kala-azar.

Haemoglobin F (HbF) levels were significantly increawd in 40 children with kala‐azar in comparison with controls (3.36 ± 2.32 versus 0.90±1.8; P<0.01). The HbF was heterogeneously distributed among the red blood cells. The glycine residue of peptides γ CN3 were within the normal umbilical cord blood range, and the haemoglobin synthesis in vitro was balanccd. After recovery from kala‐azar the HbF fell within the normal range. These results suggest that increased production of HbF is associated with accelerated erythropoiesis due to temporary marrow stress.

K Cell Activity in Acute Lymphoblastic Leukaemia of Childhood

Lymphocyte subpopulations were studied in 28 children with acute lymphoblastic leukaemia at different stages of the disease. T and B lymphocytes, present in low percentages at diagnosis, increased towards during remission in most patients. All patients off therapy had normal values of T and B lymphocytes. K cell activity, which was increased during remission in several patients, was normal in all patients off therapy. Further prospective studies will establish whether determination of K cell activity is an indicator of the stage of the disease.

Host factors against Salmonella typhi in children with glucose-6-phosphate dehydrogenase deficiency.

It is known that glucosed-phosphate dehydrogenase (G6PD) deficiency can influence the clinical symptoms in some non hemolytic diseases (1, 6, 8). It has also been observed that some diseases are more common in subjects with G6PD deficiency (5, 7, 8). Owusu et al. found that in Nigerian patients with typhoid fever the incidence of G6PD deficiency was higher than in the normal population. The reason for this predisposition to S. typhi infection remains uncertain. In this paper we report studies to define some host factors which might be related to the susceptibility of patients with G6PD deficiency in S . typhi infection. We examined ten boys varying in age from 4 to 10 years. In the past they had all suffered from hemolytic crises of favism. Ten normal children served as control subjects. No subjects had any evidence of infection at the time of study. The leukocyte bactericidal activity for S. typhi and the capacity of serum factors to promote phagocytosis of S. typlzi by normal leukocytes were studied in all