Analysis of maxillary arch expansion in growing patients treated with early Class III protocol versus RME.

Aim: To evaluate and compare the maxillary arch expansion obtained in growing patients treated with Class III early treatment protocol (the modified SEC III protocol), or rapid maxillary expansion (RME). Methods: This retrospective observational study included patients in the mixed dentition with maxillary constriction and/ or dental crowding. The first group consisted of 30 patients (11 males and 19 females, mean age 9.4 ±1.7 years) with dentoskeletal Class III malocclusion treated with the modified SEC III protocol. The second group of 30 patients (14 males and 16 females, mean age 9.3 ±1.5 years) with Class I or II malocclusion was treated with a Hyrax-type expander applied to bands on the first upper molars. For each subject, initial (T0) and post expansion (T1) digital dental casts were collected. The intermolar and intercanine widths, the arch lengths at both cusp and gingival levels, the anteroposterior length and the palatal depth were measured at T0 and T1. Results: At T1 there were statistically significant differences for 3-3 occlusal (OC) (P < 0.009), arch-length OC (P <0.030), anteroposterior arch-length (AP) (P <0.003), Depth (P <0.030) and Ap (P <0.000). No statistically significant T0-T1 changes were found between the modified SEC III and Hyrax groups except for Depth (P <0.011) with a mean difference of 2.3 mm between the two groups. Conclusions: Both bonded and banded expanders, used in the modified SEC III protocol and RME treatment respectively, produced similar changes in the upper arch. The different initial dentoskeletal malocclusions of the two sample groups were not relevant to the post-expansion arch changes.

Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.

Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.

HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation.

We report a 3-year-old Italian patient with the hyperornithinaemia, hyperammonaemia, homocitrullinuria (HHH) syndrome who presented with neurological deterioration after an intercurrent infection. Hyperammonaemia, coagulopathy and moderate hypertransaminasaemia were detected on hospital admission. Severe hepatocellular necrosis with hypertransaminasaemia (aspartate aminotransferase 20,000 UI/L, alanine aminotransferase 18,400 UI/L) and coagulopathy (PT < 5%) rapidly developed within few days, prompting evaluation for liver transplantation. A protein-restricted diet and arginine supplementation were immediately started, with a rapid improvement of the patient's neurological conditions and normalization of liver function tests and blood ammonia. The diagnosis of HHH syndrome was based on the presence of the typical metabolic abnormalities. Molecular analysis of the SLC25A15 gene showed that the patient was heterozygous for two novel mutations (G113C and M273K). The diagnosis of HHH syndrome should be considered in patients with fulminant hepatitis-like presentations. Early identification and treatment of these patients can be life-saving and can avoid liver transplantation.

Short duration of breastfeeding and early introduction of cow's milk as a result of mothers' low level of education.

Inappropriate infant feeding including a lack of breastfeeding and the early introduction of cow's milk are the most common forms of infant feeding malpractice. To evaluate the hypothesis that infant feeding malpractices are associated with mothers' low level of education, questionnaires were administered to 400 mothers of infants below 12 mo of age divided into 3 groups according to their various educational levels. Items included the type of milk given at birth and at 1, 3 and 6 mo of age. To investigate the efficacy of paediatricians in orienting infant feeding, the same questionnaire was given to 30 paediatricians in primary paediatric healthcare, in hospitals or in private practices. Initiation of breastfeeding was similar in the three groups. An analysis of the data showed that an increasing number of infants born to mothers of low and intermediate educational level did not receive exclusive breastfeeding compared with those with a higher level of education, a difference that was significant as early as 1 mo of age. In infants aged 3 mo, the prevalence of exclusive breastfeeding was 37%, 40% and 65% in the three groups, respectively, in relation to progressively increasing levels of education. In infants of 6 mo, the respective prevalence rates were 13%, 15% and 48%. Early introduction of cow's milk showed a similar correlation with educational level. A greater number of infants born to mothers with a low level of education received cow's milk at 3 mo of age compared with those born to mothers with an intermediate education (12% vs 5%). A similar difference was observed between the latter group and infants born to mothers with a high educational level (0%). This pattern was supported by data for infants at 6 mo of age with prevalence rates for cow's milk feeding of 39%, 20% and 0% in the three groups in association with progressively increasing level of educational (p < 0.05). The analysis of the paediatricians' response to the questionnaire showed that while physicians know and correctly prescribe age-related infant nutrition regimens, they are unaware that a substantial number of mothers do not comply with what they prescribe. Overall, these data support the relationship between a low educational level and infant feeding malpractice and suggest that a more effective role should be played by paediatricians in supporting an adequate duration of breastfeeding and the use of formula rather than cow's milk protein.

Deficiency of the Fas apoptosis pathway without Fas gene mutations in pediatric patients with autoimmunity/lymphoproliferation.

Fas (CD95) is a transmembrane molecule that induces programmed cell death (PCD) of lymphocytes. We examined its function in children with chronic thrombocytopenia, serum autoantibodies, and lymphadenopathy and/or splenomegaly. We found that T-cell lines from six of seven patients with this autoimmune/lymphoproliferative disease (ALD) were relatively resistant to PCD induced by monoclonal antibodies to Fas. By contrast, Fas function was normal in control patients with typical chronic idiopathic thrombocytopenic purpura (ITP) without lymphadenopathy. The defect was not due to decreased Fas expression, nor to over-production of soluble forms of Fas. Moreover, it specifically involved the Fas system because PCD was induced in the normal way by methylprednisolone. Complementary DNA sequencing of the Fas gene did not identify any causal mutation in patients with ALD. This distinguished them from patients with the human autoimmune lymphoproliferative syndrome (ALPS), who carry mutations of the Fas gene. Moreover, patients with ALD did not show the peripheral expansion of CD4/CD8 double-negative T cells that characterizes the ALPS phenotype. Fas signaling involves activation of a sphingomyelinase-catalyzing production of ceramide. We found that ceramide-induced PCD was defective in patients with ALD and not in patients with typical chronic ITP. These data suggest that the ALD patient defect involves the Fas signaling pathway downstream from the sphingomyelinase and that Fas gene mutations and double-negative T-cell expansion are not the only signs of a defective Fas system.

Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.

Programmed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30).

Prediction of intellectual deficits in children with acute lymphoblastic leukemia.

Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed.

[Role of splenectomy in Chediak-Higashi syndrome in its accelerated phase]. / Ruolo della splenectomia nella sindrome di Chediak-Higashi (SCH) in fase accelerata.

Chediak-Higashi (C.H.S.) syndrome is a rare immunodeficiency, due to defective granulocyte activity. The syndrome is characterized by large inclusion bodies in the leukocytes, albinism, photophobia, nystagmus, and recurrent infections. Some patients develop hepatosplenomegaly, lymphadenopathy, pancytopenia and widespread organ infiltrates with mononucleated cells. This phase is called "accelerated (or lymphoma-like syndrome) phase". A 5 years old girl with C.H.S. in accelerated phase received initially medical treatment without improvement. A splenectomy was performed to remove the hypersplenism and the mechanical compression of the spleen on the gut. Few days after the splenectomy the fever and the pancytopenia disappeared. The pathological examination of the spleen showed multiple intraparenchymal abscesses. Unfortunately, six months after the operation, she died after an acute episode of pneumonia, with normal hematological pattern. The splenectomy may play a role in the "accelerated phase" of C.H.S., but new treatments (bone marrow transplantation) are necessary to remove the basic disease.

Inappropriately low red cell 2,3-diphosphoglycerate and p50 in transfused beta-thalassemia.

The relationships among hemoglobin concentration (Hb), red cell 2,3-diphosphoglycerate (2,3-DPG), and p50 were studied in 20 chronically hypertransfused patients with thalassemia major. In the nontransfused control group, which included normal individuals as well as patients with sickle cell disease or iron deficiency anemia, the Hb correlated inversely with both 2,3-DPG concentration and p50, as is well established. In contrast, however, prior to transfusion, at the nadir of Hb, patients with thalassemia major had inappropriately low 2,3-DPG concentrations and p50s. These findings occurred in all patients, regardless of whether they had received packed, leukocyte-poor, or frozen-thawed red cells. The hypothesis that the time of blood storage was a factor was excluded by repeatedly transfusing one patient with packed red cells administered within 4 hr of collection in CPDA-1. A second hypothesis, that red cell function might be impaired by the iron-overloaded thalassemic environment, was excluded by studying a newly diagnosed, newly transfused patient with aplastic anemia. In both cases, the same inability to appropriately increase 2,3-DPG and p50 as the Hb fell during the intertransfusion interval was noticed. These data suggest that red cells of chronically transfused patients are unable to adapt to the decline in Hb that occurs during the intertransfusion interval.

Radiotherapy of a pseudotumor in a hemophiliac with Factor VIII inhibitor.

An 11-year-old hemophiliac with a high level of Factor VIII inhibitor (50 Bethesda units) developed a pseudotumor of the mandible. Treatment with Factor IX concentrates was unsuccessful. Since surgical management was contraindicated, the patient was given 600 rad to the mandibular lesion, which resulted in complete recovery. The authors stress that radiotherapy may be successful in pseudotumor when surgery is contraindicated.