Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities

The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a major paediatric centre over a 10 year period was examined. A total of 2468 subjects less than 2 years of age had an IgG measurement taken between July 1979 and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen patients were classified as having THI with an initial IgG level less than the fifth centile followed by a second measurement within the normal range. A further 24 patients were identified as having possible THI with a single low IgG concentration. There were 60,174 live births each year in Victoria in the years 1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and including proved and probable THI an incidence of 61 per 10(6) live births. Of those patients with proved THI 12/15 had symptoms of either atopic disease or food allergy/intolerance and three had gastrointestinal symptoms without any evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and 9/15 had IgM concentrations less than the 20th centile for age. It is suggested that in view of the preponderance of atopic and food intolerant patients that subclinical protein loss from the bowel due to allergic inflammation may be a contributing factor to the development of THI in some patients.     

The influence of recombinant human insulin-like growth factor-I (rhIGF-I) on cell growth and cytotoxicity of drugs in childhood rhabdomyosarcoma cell lines and xenograft models

Purpose: Recombinant human insulin-like growth factor I (rhIGF-I) has been reported to ameliorate vincristine-induced neuropathy, the dose-limiting side effect of this antimitotic anticancer drug. However, rhIGF-I also might have adverse effects, as has been shown in vitro, where it stimulates growth of cancer cells and protects them from cytotoxicity of anticancer drugs. The influence of rhIGF-I on the cytotoxicity of vincristine has not yet been studied. Furthermore, studies performed have been done under serum-free conditions, which are far from physiological. Methods: We studied the influence of rhIGF-I on the growth of two rhabdomyosarcoma cell lines (Rh30 and Rh1) and on the antitumor effects of vincristine, cisplatin, etoposide, doxorubicin, and topotecan under serum-free and serum-containing conditions. To extend the in vitro data, we grew Rh30 cells as xenografts in mice and determined the effects of vincristine, rhIGF-I or their combination on tumor growth. Results: In vitro, both cell lines demonstrated a functional type I IGF receptor, as shown by the rapid activation of ribosomal p70 S6 kinase after stimulation with rhIGF-I. Under serum-free conditions, rhIGF-I stimulated growth of both cell lines. Exposure to cytotoxic drugs with and without rhIGF-I resulted in higher cell numbers in cultures exposed to rhIGF-I. However, relative to the appropriate control, fractional growth inhibition and or cell kill of the cytotoxic drugs was identical with and without rhIGF-I. Under serum-containing conditions, rhIGF-I had no effect on cell growth or drug cytotoxicity. In vivo we did not find a significant influence of rhIGF-I on HxRh30 cell growth, or on the antitumor activity of vincristine. Conclusions: These studies show that rhIGF-I has no adverse effects on human rhabdomyosarcoma growth or on the antitumor effect of cytotoxic drugs under serum-containing conditions in vitro or in tumor-bearing mice. Potentially, therefore, rhIGF-I may ameliorate vincristine-induced neuropathy without adversely influencing tumor growth or vincristine cytotoxicity in children. Received: 12 February 1999 / Accepted: 21 June 1999     

Porphyria cutanea tarda-like dermatosis by hemodialysis

Summary The authors studied by electron microscope, the sun-exposed skin of the back of the hand from three heavily hemodialysed patients with a porphyria cutanea tarda-like bullous skin disease.The vascular impairment, like that of PCT, closely resembles that seen during medicamentous phototoxic processes. The connective tissue is infiltrated by large granulo-filamentous masses and the fibroblasts are secretory in appearance. At the dermal-epidermal junction, the abnormalities are important, with a diffuse infiltration of the upper dermis by a hyalin substance, probably resulting in a collagen degeneration and cellular necrosis.The aetiological factors are uncertain, as no common medicamentous factor appeared in our patients, and as the plasticizers used in the hemodialysis tubes probably played no part.

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Zusammenfassung Die sonnenexponierte Haut der Handrücken von drei Hämodialysepatienten mit einer Porphyria cutanea tarda-ähnlichen Dermatose wurde elektronenmikroskopisch untersucht. Die Gefäßveränderungen entsprechen denen, die während eines medikamentösen phototoxischen Prozesses mit PCT beobachtet werden.Das Bindegewebe ist mit granulo-filamentösem Material infiltriert und die Fibroblasten befinden sich im aktivierten sekretorischen Zustand. Im Bereiche der dermal-epidermalen Grenzzone sind diese Veränderungen besonders ausgeprägt, wobei eine diffuse Infiltration der oberen Dermis mit einer Hyalinsubstanz — offenbar das Resultat einer Kollagendegeneration — und einer cellulären Nekrose vorliegt.Die ätiologischen Faktoren sind ungewiß, da keine besonderen Medikamente bei den Patienten gegeben wurden und das Kunststoffmaterial, welches bei den Hämodialysegeräten verwandt wird, wohl keine Rolle spielt.