A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant.

Post-transplant diabetes mellitus (PTDM) and impaired glucose tolerance are now considered among the major adverse events following organ transplantation. The present study was aimed at investigating the regulation of glucose metabolism in pediatric recipients of a kidney transplant (KT), receiving tacrolimus or cyclosporine A-based immunosuppression. Twelve subjects, eight males and four females, aged 12.1+/-3.8 yr, and with a mean time from KT of 45.6 months were enrolled in the study. All patients had a basal evaluation of fasting glucose (GF), fasting insulin (IF), C-peptide and glycated hemoglobin (HbA1c) levels. They then underwent oral glucose tolerance test (OGTT), with measurement of blood glucose and insulin concentration. Two children had impaired GF, associated with supernormal HbA1c levels, one patient showed impaired glucose tolerance, none had PTDM. Peripheral insulin resistance, as measured by quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment estimate of insulin sensitivity (HOMA-IR) index, was enhanced in 3 patients. Subsequently, GF significantly increased with time from transplant (p=0.01), while fasting C-peptide and the area under the curve of insulin correlated with creatinine clearance. In conclusion, our results, although generated in a small sample size, would suggest that long-term follow-up of children receiving a KT should extend to explore the response to oral glucose load and at least the basal measure of insulin response.

TNP-470 and recombinant human interferon-alpha2a inhibit angiogenesis synergistically.

The hypothesis that the combination of two known antiangiogenic agents TNP-470 and interferon (IFN)-alpha exerts synergistic effects has been investigated in vitro and in vivo. In vitro, TNP-470 and recombinant human IFN-alpha2a (rhIFN-alpha2a) resulted in a dose-dependent inhibition of proliferation of human umbilical vein endothelial cells (HUVECs) and EA.hy926 endothelial cells. Compared with the two agents used singly at their lowest or ineffective doses, combined treatment with the same doses inhibited more intensely in the absence of cytotoxicity and displayed similar behaviour on cell chemotaxis and capillary morphogenesis on Matrigel. However, the secretion of matrix metalloproteinase 2 (MMP-2) and MMP-9 was not influenced by the two agents, either alone or in combination, even when they were applied at their lowest efficacious doses or at higher cytotoxic doses. Experiments in vivo with the chick embryo chorioallantoic membrane (CAM)-sponge assay revealed the same dose-dependent inhibition and synergy. As the basic fibroblast growth factor (bFGF)-induced angiogenesis in the CAM-sponge model was strongly inhibited by the combined treatment, TNP-470 and rhIFN-alpha2a would appear to exert antiangiogenesis synergistically, perhaps by interfering with the bFGF-mediated pathway.

[Long-term effects of combined therapy in patients with beta-thalassemia major]. / Effetti a distanza della terapia combinata in soggetti affetti da beta-thalassemia major.

We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

[Measurement of the spontaneous growth hormone increase in short children. Diagnostic significance and neuroendocrine implications]. / Valutazione dell'increzione spontanea di ormone della crescita in bambini con bassa statura. Significato diagnostico e implicazioni neuroendocrine.

The assessment of growth hormone deficiency (GHD) in children with growth retardation is frequently difficult. The diagnostic reliability of standard pharmacological GH provocative tests has been questioned and several investigators have focussed on measurement of spontaneous GH secretion at frequent intervals over periods of 12-24 hours, with mathematical analysis of resulting secretory patterns. The aim of our study was to assess GH secretion in children with growth retardation, either in prepuberal and puberal ages, in order 1) to evaluate the diagnostic relevance of spontaneous GH secretion in comparison to tests, and 2) to gain neuroendocrine interpretations of GH secretion. We investigated 58 short children (height < 5th centile), 35 males, aged 6.4-15 years, without chronic diseases or dysmorphic syndromes. All subjects were divided into 3 groups, either in prepubertal and pubertal ages: normal (normal growth rate, within -0.80 HVSDS; normal GH peak after standard clonidine test > 7 ng/ml; 15 prepubertal, 8 pubertal); slow-growing (growth rate lower than -0.80 SDS; normal GH peak to test; 13 prepubertal, 13 pubertal); GH deficit (growth rate lower than -0.80 SDS; GH peak to test < 7 ng/ml; 6 prepubertal, 3 pubertal). In all children spontaneous GH secretion was evaluated for 24-hrs, 12-hrs daily and 12-hrs overnight, sampling every 30 minutes. The results were analyzed by the PULSAR computer program to determine number, height, area and amplitude of pulses and the baseline and GH secretory areas under and over baseline.(ABSTRACT TRUNCATED AT 250 WORDS)