Roughening of k-mer-growing interfaces in stationary regimes.

We discuss the steady-state dynamics of interfaces with periodic boundary conditions arising from body-centered solid-on-solid growth models in 1+1 dimensions involving random aggregation of extended particles (dimers, trimers, ...,k-mers). Roughening exponents as well as width and maximal height distributions can be evaluated directly in stationary regimes by mapping the dynamics onto an asymmetric simple exclusion process with k-type of vacancies. Although for k≥2 the dynamics is partitioned into an exponentially large number of sectors of motion, the results obtained in some generic cases strongly suggest a universal scaling behavior closely following that of monomer interfaces.

Recombinant growth hormone treatment in short patients with thalassemia major: results after 24 and 36 months.

Treatment with recombinant growth hormone (rhGH), 0.6 IU/kg/week s.c., previously successfully conducted for one year, was continued in 15 (Group A) and 8 (Group B) short thalassemia major patients with reduced GH reserve, for two and three years, respectively. In Group A, height for chronological age (Ht SDSCA) increased significantly (p = 0.021) from the start of treatment, but the positive effect was only apparent because of the concomitant slight worsening of height for bone age (Ht SDSBA). Median deltaHt SDSCA/deltaHt SDSBA was <1.0 with respect to both the start (0.87) and the end of the first year of rhGH therapy (0.89). IGF-I levels increased significantly (p = 0.043) compared with values both at the start and at the end of the first year of rhGH therapy. In Group B neither Ht SDSCA nor Ht SDSBA differed statistically from starting values, the former having a positive trend and the latter a negative one. Median deltaHt SDSCA/deltaHt SDSBA was 0.92 with respect to the start, and 0.94 with respect to the end of the second year. IGF-I levels increased significantly (p = 0.043) with respect to starting values. Our data show that the encouraging results described from the first year of rhGH treatment did not persist during the second and third years, and we conclude that this is because increase in bone age with continued treatment is equal to, or slightly greater than the height age increase. We propose that patients with thalassemia major with short stature should receive rhGH treatment for only one year, and that more prolonged treatment should be reserved for selected adolescents who have psychological problems due to shortness; for these patients growth acceleration could represent the main goal, even if this leads to a substantially unchanged or slightly decreased final height.

[Congenital fetal neuroblastoma]. / Neuroblastome congénital foetal.

Neuroblastoma are pediatric tumors of neural crest origin, most often localized in adrenal glands and infrequently congenital. We report two fetal cases found at autopsy, performed at 24 and 28 weeks of gestation, respectively. The 24 week old fetus did not show any malformation; systematic histological analysis found neuroblastoma cells in both the adrenal glands and the retroperitoneal fat tissue. The 28 week old fetus was hydropic and exhibited a nodule (3 cm) in the posterior mediastinum, next to the thoracic spinal cord. This tumor responded to a neuroblastoma associated with small metastatic foci in the adrenal glands, the liver and the frontal brain cortex. The placenta was abnormally heavy and showed hemorrhagic and necrotic areas. Microscopically plugged clumps of neuroblastoma cells were found inside fetal vessels. Immunohistochemistry was employed in both cases and the cells showed immunoreactivity for NSE, NB 84, chromogranin, synaptophysin and neurofilaments, while desmin, MIC 2, and protein S-100 were negative. Congenital neuroblastomas are rare and, to our knowledge this is the thirteenth report of congenital neuroblastoma associated with placental metastasis.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Diamond-Blackfan anaemia in the Italian population.

Diamond-Blackfan anaemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation: 30% of patients have congenital malformations. The link between these malformations and defective erythropoiesis is unclear: a defect in a molecule acting both on embryo development and haemopoiesis has been proposed. Inheritance is autosomal dominant in most familial cases, but recessive families have also been reported. Many cases are sporadic. A DBA locus has been mapped on chromosome 19q13.2 (Gustavsson et al, 1997), but several families unlinked to this locus have also been reported (Gustavsson et al, 1998). This paper presents clinical, epidemiological and molecular data for DBA in the Italian population. Segregation analysis of 19q markers in patients with DBA showed exclusion of this locus in 5/12 families with inherited DBA. There was evidently locus heterogeneity for DBA in this population. A new microdeletion was identified in one patient. Other families, in which DBA segregates concordantly with the 19q critical region, suggest incomplete penetrance and expressivity of the DBA gene.

Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR).

Thrombocytopenia with absent radii (TAR) is a rare autosomal recessive disease characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. We performed mutational screening of coding and promoter regions of the c-mpl gene, encoding thrombopoietin (TPO) receptor, by sequence analysis in four unrelated patients affected by TAR syndrome. Our results indicate that c-mpl gene mutations are not a common cause of thrombocytopenia in TAR syndrome.

pQCT (quantitative peripheral tomography) and data evaluation of phosphocalcic metabolism in thalassaemic patients.

pQCT is a method which allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. 21 thalassaemic patients (8 females, 13 males) aged from 10 to 32 years, were examined using pQCT at the ultra distal radius to evaluate SSI (Stress-Strain Index). ALP, serum calcium, hydroxyproline, magnesium, IGF-I, and body surface were determined. The results show a good correlation between cortical BMD and age, concentration of hydroxyproline in urine, serum bone Gla protein, body surface index, bone density of trabecular bone and SSI. Good correlation was found between trabecular bone density and age, IGF-I, BGP and PTH, and between SSI and cortical BMD, age and BSI. The linear relationships between age and cortical and trabecular density show an increase of cortical BMD with age and a decrease of trabecular density with age. The same results were obtained considering trabecular and cortical density versus SSI.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

[Idiopathic thrombocytopenic purpura and food allergy: a study on possible correlations]. / Porpora trombocitopenica idiopatica ed allergia alimentare: uno studio sulle possibili correlazioni.

UNLABELLED: Eight children affected by idiopathic chronic thrombocytopenia were studied for history of food allergy, anti-platelet antibodies, total IgE, prick test for food antigens, AGA and EMA. They were free of treatment for thrombocytopenia since at least six months before. Three children had in the first year of life intolerance to cow's milk proteins with atopic dermatitis and/or poor growth. None had AGA or EMA positivity. 6/8 had positivity for anti-platelet antibodies. A 15-days oligoantigenic diet was instituted in all of them. Platelet count was unaffected in all but one, in which a sharp increase was noted (from 19x 10(9)/l. to 150x 10(9)/l.). He was a 12-year-old boy with a previous history of cow's milk intolerance and actual skin prick test positivity for casein and lactoglobulin. A one-year follow up for this case was instituted and he was put on two further 15-days periods of oligoantigenic diet, but no change in platelet count was noted any more. CONCLUSION: we were not able to correlate chronic thrombocytopenia to food allergy.

Long-term GnRH-agonist administration revealed a GnRH-independent mechanism stimulating FSH discharge in humans.

The present study evaluated the FSH and LH episodic discharge in different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks; Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration; this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared, FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.

Primary hypergammaglobulinemic purpura associated with IgG2 deficiency. A case report.

Hypergammaglobulinemic purpura is a rare disease in children. We report a case of a 12 year-old girl with a history of frequent infections. We found the presence of IgG2 deficiency despite polyclonal hypergammaglobulinemia. An IgG subclass determination should be obtained in every child with polyclonal hypergammaglobulinemia and features of immunodeficiency.

[Beta-cell secretion in patients with thalassemia major]. / Secrezione beta-cellulare nei pazienti con thalassemia major.

Diabetes mellitus is one of the main endocrinological disease complicating the course of thalassemia major. This study aimed evaluate beta-cell secretion in 24 patients with thalassemia major attending the hematological Day Hospital at the Pediatric Clinic in Modena where transfusion therapy is performed in all thalassemic patients so as to maintain minimum hemoglobin levels above 10.5 g/dl, together with intensive ferrochelating therapy (desferrioxamine 50-60 mg/kg/die s.c. 6 days a week). A C peptide challenge with glucagon was performed in three patients already receiving insulin therapy for diabetes mellitus; this unexpectedly revealed a slight residual beta-cell secretion. An intravenous glucose tolerance test (IVGTT) was performed in the remaining 21 non-diabetic patients, with widely varying findings regarding insulin secretion: from below 50 microUl/ml in 5 patients to above 200 microUl/ml in 5 patients, and between 50 and 150 microUl/ml in the remaining 11 patients. This study therefore confirmed that insulin secretion frequently alters in thalassemic patients. Moreover, insulin secretion is not correlated to ferritinemia or influenced by familiar diabetes or patient age.

Evidence suggesting an additional control mechanism regulating episodic secretion of luteinizing hormone and follicle stimulating hormone in pre-pubertal children and post-menopausal women.

The possible differential regulation of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion in pre-pubertal children and in post-menopausal women was investigated. Children were studied for 4 h and post-menopausal women for 6 h; blood samples were taken every 10 min. Post-menopausal women were studied before and 21 days after administration of a single i.m. dose of gonadotrophin-releasing hormone (GnRH) analogue. Eight post-menopausal women and 18 children (nine boys and nine girls) were enrolled. The children were divided into two groups: A, at Tanner stages 0-1 (four boys and three girls); B, at Tanner stage 2-3 (five boys and six girls). Plasma LH and FSH concentrations were determined using an immunofluorimetric assay. Time series were analysed and the specific concordance (SC) index was computed to determine the degree of concordance between episodes of LH and FSH secretion. While children of group A had LH concentrations below the minimal detectable dose of 0.1 IU/l, group B showed measurable LH plasma concentrations (1.4 +/- 0.3 IU/l, mean +/- SEM). Plasma FSH concentrations were detectable in both groups. Group A showed FSH plasma concentrations significantly lower than those of group B (0.75 +/- 0.2 and 1.95 +/- 0.4 IU/l respectively; P < 0.05), but FSH pulse frequency was higher in group A (P < 0.05). Children of group B showed significant concomitance of LH and FSH secretory events at time 0 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.

The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of high-dose intravenous immunoglobulins in pediatric hematology]. / L'uso di immunoglobuline endovena ad alte dosi in ematologia pediatrica.

High-dose intravenous immunoglobulin play a critical role in a lot of pediatric hematologic diseases. In our experience we studied the effects of IVIG treatment in 63 children. They all tolerated IVIG preparations in every infusions; no trouble caused the interruption of treatment. The efficacy is evident in immunomediated diseases, most of all ITP, and controlling septic episodes in immunocompromised patients (ALL, AIDS, marrow bone transplantation). An important problem is the cost of preparation; but we may consider that this treatment, for example in ITP, reduces hospitalization for children, necessity of platelets' transfusions, use of steroids and, therefore, their collateral effects. Hence, we assert that the social cost of the management of ITP disease is not higher in children treated with IVIG. Furthermore, short hospitalization for IVIG therapy contributes to accept this disease. It should be advisable to make controlled studies to define with more accuracy the role of this preparation and the modality of its use in the different clinical conditions in which it is employed.

Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children.

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.

Reduced spinal bone density in young women with amenorrhoea.

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

A rise in haemoglobin levels may enhance serum triiodothyronine (T3). Concentrations in prepubertal patients with beta-thalassaemia major.

The aim of the present study was to investigate the effects of increased haemoglobin (Hb) levels on the thyroid function in patients with beta-thalassaemia major. Basal levels of thyroid hormones (T4, T3) and free thyroid hormones (fT4, fT3), basal TSH concentrations and the TSH responses to a TRH bolus (0.2 mg iv) were studied in ten euthyroid thalassaemic patients, aged 8 to 19 years, and in one 12 years-old thalassaemic girl with primary hypothyroidism. Five euthyroid thalassaemic patients (aged 8 to 12 years), as well as the hypothyroid thalassaemic girl, were prepubertal, whereas five euthyroid thalassaemic patients (aged 15 to 19 years) had delayed puberty. In each patient, the endocrine evaluation was carried out under conditions of low Hb levels (31 days after the last blood transfusion, mean Hb = 9.8 +/- 1.5 g/dl), and 11 days after the transfusion of 2 units packed red blood cells (PRBC). The latter increased significantly Hb concentrations in all the thalassaemic patients (mean Hb = 12.8 +/- 2.5 g/dl, P less than 0.001). Twelve normal prepubertal subjects, aged 6 to 11 years, served as the control group. Before the PRBC transfusion, basal T4, T3, fT4, fT3 and TSH concentrations were similar in euthyroid prepubertal thalassaemic patients (EPT) and in euthyroid patients with delayed puberty (EDPT), and were comparable to those in control subjects. The TSH responses to TRH (TSH peak, area and delta area) observed in EPT patients were similar to those in the EDPT group, but significantly higher in comparison with the normal children.(ABSTRACT TRUNCATED AT 250 WORDS)