[Insulin and glucagon plasma levels in very low birth weight preterm infants of appropriate weight for gestational age]. / Livelli plasmatici di insulina e glucagone in neonati pretermine di peso molto basso appropriato per l'eta gestazionale.

OBJECTIVES: Prematurity is a known risk factor for hypoglycaemia, hyperglycemia, neonatal sepsis and other common neonatal complications, possibly associated with glucoregolatory hormone (insulin and glucagon) alterations. Insulin and glucagon levels change also in relation to gender, mode of delivery and postnatal clinical severity. Because of the lack of reference range in literature, the aim of this study is to assess plasma insulin and glucagon levels in preterm appropriate for gestational age (AGA) infants of birth weight <1500 g (very low birth weight, VLBW) as a function of gestation, birth weight, gender and mode delivery. METHODS: The authors examined 48 preterm AGA infants (mean birth weight 1 163+/-286 g, mean gestational age 28.2+/-2.4 weeks). The infant population was subdivided in relation to gestational age, weight, gender, mode of delivery and assisted ventilation at 5-7(th) days. Plasma glucose, insulin and glucagon levels were assessed in all newborns at birth and at 5-7(th) days of life. Data were analyzed using t-test. RESULTS: A negative correlation between insulin and gestational age was observed (P<0.05). At birth, no significant differences regarding plasma glucose, insulin and glucagon levels were observed as a function of the examined category variables. At the 5-7(th) days of life, insulin levels were significantly higher in newborns with gestational age =or<27 weeks (P<0.02), in the female gender (P<0.02) and in the infants born to emergency Cesarean delivery (P<0.05). CONCLUSIONS: These findings indicate potentially useful reference range values for plasma insulin and glucagon in the VLBW population.

Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth.

BACKGROUND: An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. METHODS: A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15 wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had significantly increased cortisol on d-1 ( approximately 5.2-folds) [median: 18.95 (95% CI: 11.20-39.4) microg/dl vs. 3.66 (1.94-6.82) microg/dl, p < 0.0001)] and d-7( approximately 1.7-folds) [12.0 (4.39-22.97) microg/dl vs. 7.8 (3.63-12.8) microg/dl, p = 0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 ( approximately 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p = 0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR = 14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile (OR = 4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant at univariate analysis). CONCLUSIONS: Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.

Non protein bound iron concentrations in amniotic fluid.

OBJECTIVES: To investigate whether amniotic fluid concentrations of non protein bound iron (NPBI) vary with growth in healthy fetuses and also offer a reference curve in the second trimester of pregnancy. DESIGN AND METHODS: Amniotic fluid concentrations of NPBI were measured by HPLC in 118 women with physiological singleton pregnancies, who underwent amniocentesis for fetal karyotype between weeks 15 and 18 of gestation. RESULTS: NPBI increased progressively from weeks 14--15 to weeks 15--16, peaking at 17--18 weeks of gestation. NPBI values regressed positively with gestational age (GA). Multiple linear regression analysis between NPBI, as dependent variable, and various fetal parameters, as independent variables, showed a statistically significant regression coefficient with GA, bi-parietal diameter and transverse cerebellar diameter. CONCLUSIONS: The present data constitutes the first quantification of NPBI concentrations in amniotic fluid under physiological conditions. Correlations with GA and ultrasound fetal biometry suggest that NPBI may play a role in fetal growth.

Effect of blood transfusions on oxidative stress in preterm infants.

OBJECTIVE: To confirm the increase in non-transferrin bound iron (NTBI) after packed red cell (PRC) transfusion and to evaluate the association with increased oxidative stress in preterm infants. METHOD: Twenty healthy preterm infants (gestational age 28.2 (2.2) weeks; birth weight 1047 (230) g), who required blood transfusion for anaemia of prematurity were prospectively studied. Serum concentrations of NTBI, total hydroperoxides (TH), and protein SH groups, and plasma total radical trapping antioxidant capability (TAC) were measured within three hours before and after PRC transfusion. The infants were transfused with 38.6 (23) ml PRCs over 5.8 (1.0) hours, at a mean age of 43.3 (25.1) days. RESULTS: After PRC transfusion, haemoglobin concentration increased from 9.2 (1.1) to 14.6 (1.5) g/l. Mean plasma NTBI concentration after transfusion was significantly higher (0.43 (0.45) v 2.03 (1.31) micromol/l; p = 0.001), while plasma concentrations of TH (212.3 (42.2) v 214.7 (66.3) Carr units/l) and protein SH groups (317.5 (38.8) v 353.8 (57.4) micromol/), and TAC (256.3 (36.1) v 267.1 (42.4) micromol HClO/ml) remained unchanged. CONCLUSION: For three hours after PRC transfusion, plasma NTBI is significantly increased in preterm infants, but this is not associated with significant changes in oxidative stress.

Production of parathyroid hormone and parathyroid-hormone-related protein by breast cancer cells in culture.

Parathyroid-hormone-related protein (PTHrP) has been implicated in the origin of malignant hypercalcaemia. However, PTHrP production is not restricted to neoplastic cells, it is widespread among a variety of normal cell types and tissues. A physiological role for PTHrP has not been well defined. We describe a case of breast cancer with bone metastases and humoral hypercalcaemia of malignancy, with high levels of plasma C-terminal parathyroid hormone (PTH), mid-molecule PTH and PTHrP. Cells from breast cancer biopsies were cultured and medium samples assayed for the C-terminal and mid-molecule fragments, intact PTH and PTHrP. The data indicate a progressive increase in both PTH fragments and PTHrP levels, over a period of 30 days. No temporal parallelism exists between PTH fragments and PTHrP concentrations, the former being maximum at the 14th day, and the latter at the 30th day from the beginning of the culture. Our results indicate a coproduction of PTH and PTHrP by the breast cancer cells both in vivo and in vitro.

Treatment of bone metastases with dichloromethylene bisphosphonate.

PURPOSE: The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS: Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS: Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS: We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

Comparison between CEA, TPA, CA 15/3 and hydroxyproline, alkaline phosphatase, whole body retention of 99mTc MDP in the follow-up of bone metastases in breast cancer.

The development of bone metastases in cancer can be monitored easily using three markers: 24 h urinary hydroxyproline excretion (HOP) (an index of osteoclastic activity), serum alkaline phosphatase (Alk.Ph.) (an index of osteoblastic activity) and 24 h whole body retention of 99mTc-methylene diphosphonate (WBR%) (an index of bone turnover). To evaluate the effectiveness of this group of bone tumor markers in breast cancer we compared it with the following group of three markers which are commonly used in the monitoring of breast cancer and in the follow-up of advanced disease with or without bone metastases: carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast carcinoma antigen (CA 15/3). In 48 patients with bone metastases CEA, TPA and CA 15/3 were shown to be sensitive (79%, 85%, 90% respectively), while HOP, Alk.Ph. and WBR%, which are commonly accepted as reliable markers of bone activity, showed a lower sensitivity (67%, 46%, 75% respectively). These results may be explained by the lack of osteoclastic or osteoblastic (or both) activity at the time of diagnosis. This explanation is supported by the fact that the bone markers HOP, Alk.Ph. and WBR% were found to be more sensitive than the others in the subsequent follow-up study. We conclude that in our study, CEA, TPA and CA 15/3 are at first more sensitive than Alk.Ph., HOP and WBR% but during the follow-up Alk.Ph., HOP and WBR% are possibly both more specific and more sensitive.