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Objectives:Scope of this analysis was to estimate the cost-effectiveness of rituximab maintenance (r-maintenance) therapy vs. observation, in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from a large multicenter study, in the Italian public payer’s perspective.

The aim of this study is to extend to pre-school ages the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP)-2002 growth charts for height, weight and body mass index (BMI), to obtain charts (SIEDP-2006) that apply to the Italian population from 2 to 20 yr of age, taken as a whole, or separately in two geographical areas (Central-North Italy and South Italy). The charts are based on a sample of about 70,000 subjects attending infant, primary and secondary schools, between 1994 and 2004. The distribution of the sample by gender, age and geographic area was roughly similar to that of Italian school population in the last decade of the 20thcentury. Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP-2006 references are presented both as centiles and as LMS curves for the calculation of SD scores, and include the extra-centiles for overweight and obesity. Large differences in BMI growth pattern emerged between the SIEDP-2006, 2000 CDC and UK90 references: in Italy, BMI is higher and its distribution is more skewed during childhood and adolescence. At the end of growth, median values of the three references are similar, but the 97thcentile of 2000 CDC charts is much higher and increases more steeply than that of SIEDP-2006 charts, which on the contrary reach a plateau. SIEDP-2006 references intend to supply pediatricians with a tool that avoids the use of charts that are outdated or that refer to other populations, and thus should be suitable for adequately monitoring the growth of their patients.

Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormalities consisted of two balanced translocations (15;18 and 8;15), three unbalanced ones (15;18, 15;19, and 9;15), and one interstitial deletion of bands 15q11 and q12. The seventh case had an unidentified extra chromosome. These data and a review of the literature led to the conclusion that deficiency, transposition, and even duplication of the region(s) 15q11-q13 may all result in a syndrome which is identifiable with or similar to the Prader-Willi syndrome.

Two 46,XX sibs, one of female, one of male gender, and both with ambiguous external genitalia and ovotestis, were H-Y positive. The mother was H-Y negative. It is assumed that the underlying mutation was transmitted by the father, resulting in an autosomal dominant mode of inheritance. The common origin and the nature of the mutation leading to XX sex reversal are discussed.

HLA genotype and HLA-linked marker data for 40 unrelated patients from central Italy and 2 unrelated patients from Sardinia with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) were analyzed. The results confirm that the HLA-linked 21-OH-def gene is associated with several different HLA determinants and complete HLA haplotypes, although the only determinant with significantly increased frequency was the complement C2 allele C2B. The HLA antigens B8 and DR3 were found in significantly decreased frequencies. The haplotype A3, Cw6, Bw47, BfF, DR7, which is exceptionally rare in the general population but which has been found in many other 21-OH-def patients from diverse geographical origins, was also found in one of the Italian patients. This and other HLA haplotype associations found among the Italian patients may represent mutations that have occurred on HLA haplotypes with genetic linkage disequilibrium or, alternatively, may represent mutations that have not yet had time to become randomly associated with different HLA complex determinants. The marked negative associations with B8 and DR3 could, however, result from an interaction between the gene products of the HLA complex and the 21-OH-def phenotype.

A ring 12 chromosome was found in a male child with minor phenotypic alterations. No obvious loss of chromosome material was detected. Since there is no other case of a ring 12 in the literature, it was not possible to determine whether the phenotype was due to (invisible) terminal deletions or to karyotypic variation. In lymphocyte cultures 9% of the cells had either no or two rings, but the patient’s RBC had normal activities of the enzymes lactate dehydrogenase B and peptidase B, whose loci are located on the proximal portions of 12p and 12q, respectively. Dicentric rings were found in 37 cells, and all had two active centromeres, in contrast with the relatively frequent finding of latent centromeres in translocated dicentric autosomes. Two latent centromeres were found in one tricentric “rod-shaped” open ring 12, probably derived from a tetracentric ring. It is postulated that latent centromeres are rare in ring chromosomes because, if consistent suppression of centromeres in excess of one took place at each duplication, rings with four, eight, or more centromeres would be formed rather frequently, which is not the case.

A male child and his mother who are nullisomic and monosomic, respectively, for the distal portion of Xp because of an unbalanced X-Y translocation were tested for steroid sulfatase activity after clinical examination had yielded evidence for ichthyosis in the boy. Deficiency of steroid sulfatase was found in the male patient, while in his mother enzyme levels were in the heterozygous range. These results, based on cytogenetic evidence obtained with an elongation technique, indicate that the STS locus is at Xp223.

Prognosis for PTCL patients is poor; the 5-year overall survival rate ranges from 25 to 40%. Despite variable CD52 expression in T-cell malignancies, promising results have been demonstrated with alemtuzumab (Campath ®). We report preliminary results of standard CHOP therapy plus alemtuzumab (CHOP-C) in a cohort of untreated PTCL patients (pts). Beginning Jan 03, 25 consecutive PTCL pts were treated with 8 courses of CHOP. In the first cohort, 4 pts received alemtuzumab 30 mg. sc 1 day prior to the first 4 courses of CHOP, whereas in cohort 2 (N=21) alemtuzumab 30 mg was given one day prior to all 8 CHOP courses administered. The histopathology was centrally reviewed and included 16 patients with PTCL-U, 6 patients with AILD-T, and 3 patients with ALCL Alk. CD52 expression was checked by immunohistochemisty on paraffin-embedded material. Median age of patients was 51.2 years (range: 28–69), 22 (88%) were stage III–IV, 3 (12%) had bulky disease, 11 (44%) had bone marrow involvement, and 13 (52%) had high LDH values. The age-adjusted IPI values were 0 in 5 pts, 1 in 8 pts, 2 in 9 pts, and 3 in 3 pts. All 25 pts completed therapy. Results: at a mean follow-up of 436 days (range:105–1124) 14/25 pts. are still alive and 11/25 have died, mostly of progressive disease (10/11). 17/25 pts achieved CR, 1 PR and 1 minimal response (MR); 6 pts. progressed. Of these 6 pts, 1 pt achieved a PR, and 1 pt in MR and 2 pts in CR died despite salvage treatment; one patient died +198 d. in CR due to pneumonia. Three pts relapsed +62, +119 and +145 days after achieving a CR. The mean duration of response was 273 days. The 2-year OS and FFS (Failure Free Survival) were 45% and 50% days, respectively (Figure). CD52 expression was available for 16 of 25 pts. Of 11 pts who progressed on, or relapsed after therapy, CD52 was positive in 5, negative in 2 and not available for 4 pts. Among the 14 responding pts, 7 were positive, 2 negative, and not available in 5. Conclusions: CHOP-C seems to be a feasible chemoimmunotherapy regimen: the efficacy of this therapy seems fairly good with a CR rate of 68%; however 6/25 pts showed disease progression during therapy, most frequently after the third C-CHOP course. Although most pts were positive for CD52 expression (12/16), no relationship between CD52 expression and treatment outcome was identified. Failure free survival (25 pts.) Failure free survival (25 pts.)

Prognosis for PTCL patients is poor; the 5-year overall survival rate ranges from 25 to 40%. Despite variable CD52 expression in T-cell malignancies, promising results have been demonstrated with alemtuzumab (Campath ®). We report preliminary results of standard CHOP therapy plus alemtuzumab (CHOP-C) in a cohort of untreated PTCL patients (pts). Beginning Jan 03, 25 consecutive PTCL pts were treated with 8 courses of CHOP. In the first cohort, 4 pts received alemtuzumab 30 mg. sc 1 day prior to the first 4 courses of CHOP, whereas in cohort 2 (N=21) alemtuzumab 30 mg was given one day prior to all 8 CHOP courses administered. The histopathology was centrally reviewed and included 16 patients with PTCL-U, 6 patients with AILD-T, and 3 patients with ALCL Alk. CD52 expression was checked by immunohistochemisty on paraffin-embedded material. Median age of patients was 51.2 years (range: 28–69), 22 (88%) were stage III–IV, 3 (12%) had bulky disease, 11 (44%) had bone marrow involvement, and 13 (52%) had high LDH values. The age-adjusted IPI values were 0 in 5 pts, 1 in 8 pts, 2 in 9 pts, and 3 in 3 pts. All 25 pts completed therapy.

Bone mineral content of subjects with Turner's syndrome has been found smaller than predicted by age and sex. Bone mineral content related to bone width (BMC/BW) of 19 patients with Turner's syndrome not yet receiving estrogen replacement therapy (mean age: 11 yrs;range: 6-15 yrs) and of 22 patients receiving exogenous estrogens (mean age: 17 yrs 7/12; range: 11 yrs 8/12-28 yrs 4/12) was evaluated by single photon absorptiometry of distal forearm. In both groups BMC/BW was significantly reduced (p < 0.025 and p < 0.0001 respectively )when compared with normal subjects. Seven patients with Turner's syndrome, in whom estrogen replacement therapy had begun at a chronological age less than 14 yrs, have been examined longitudinally to evaluate the role of estrogens in bone mineralization. The average increase in BMC/BW was 11% and 7% at 6 and 18 months respectively, after the beginning of therapy. However, the BMC/BW values remained below normal. Our data confirm a deficit in bone mass in patients with Turner's syndrome; bone demineralization is present also at prepubertal age. In our experience, precocious estrogen treatment (11-14 yrsl can improve bone mass in patients with Turner's syndrome.

Somatostatin (GHRIH) could be helpful in the treatment of diabetes mellitus when high levels of growth hormone and glucagon interfere with the metabolic control. In obese children the i.v. injection of 3 ug/kg of ideal body weight of GHRIH before i.v. glucose tolerance test lowered significantly the glucose disappearance rate, the plasma insulin levels, and delayed the peak value. In diabetic children the i.v. administration of 3 μg/kg of GHRIH over two min, followed by a 60 min infusion of 7 μg/kg in saline solution induced a significant decrease of blood sugar, growth hormone and glucagon levels; the administration of 3 μg/kg of CHRIH immediately before a standardized physical exertion significantly reduced the rise of growth hormone levels. GHRIH can open new possibilities in the treatment of juvenile diabetes, at least after puberty.

Almost 5% of women is affected by irsutism and about 55% of these subjects start complaining on some signs during the adolescence period in which a considerable anxiety is connected with the body image. After having excluded Cushing's syndrome, CAH late onset, ovarian and adrenal turnours, we treated six adolescents (mean age 16yr 1mo)affected by hirsutism (Hatch's score ≥ 10) with 100 mg/daily of spironolactone for 12 months (200 mg/daily with score > 20 or therapeutical unsuccess after 6 months of therapy). To all subjects was added an oral contraceptive (0.15 mg of descgestrel + 0.03 mg of ethinil -estradiol) to obtain regular withdrawal bleeding and contraception effect. To make a correct evaluation of the data, we excluded from the study those areas treated by esthetic treatment. Clinical and hormonal evaluations (FSH, LH, PRL, T, DHEAs) were obtained before and after 3-6-9-12 months of therapy. During follow-up no change was demonstrated in hormone levels; the mean score significantly decreased after 3 months of therapy (p < 0.01) and at every specific control (p < 0.001). In one girl, 6 months off-therapy, no sign of hirsutism was demonstrated. No significant side-effects were noted in our patients. Spironolactone combined to an cstro-progestagen is an effective and well-tolerated approach to the smanagement of hirsutism in adolescents.

Fifteen subjects with chromosome mosaics were investigated: in ten of them a chromosome pattern 45,X/46,X,i dic(Yp) was found, in four 45,X/46,X,i dic(Yq), in one 45,X/46,X,Yq+.; the ratio of the two cell types varied between patients and between different tissues. The phenotype of patients ranged from female with some Turner's syndrome stigmata, to infants with ambiguous external genitalia, to azospermic male. Most patients presented short or very short stature. Laparatomy and hystologic studies revealed hypoplasic or dysgenetic or ever normal testes and streak gonads variously combined; four patients were tested for H-Y antigen anc found to be positive-reduced. No correlation was demonstrated between clinical data and chromosomal pattern. Phenotypic feature of mosaics with structurally abnormal Y-chromosomes are not different from feature found in 45,X/46,XY patients; probably no genetically active portion of Y is lost. The different proportion of 45,X cells in various tissues possibly has the greatest influence on the phenotype of these subjects.This investigation was performed in collaboration with the Institute of General Biology and Genetics, University of Pavia.

HLA typing was performed in a family with a child affected by salt-wasting CAH due to 21-OH deficiency. Father,mother, sister were clinically normal, with absence of signs of virilization or salt-wasting symptoms, normal stature and fertility. Based on the linkage of the gene for 21-OH deficiency to the HLA complex, the sister resulted heterozygous for the gene of CAH:Three heterozygous members were therefore found in this family: father,mother,sister. Heterozygous carriers of the CAH-gene are expected to have normal baseline hormone levels.On the contrary father and sister were found to have abnormally elevated hormone levels, even if clinically normal.Both have the CAH gene-linked haplotype (“a” in father, “c” in sister) and the “b” haplotype. It is speculated that the biochemical abnormalities in absence of clinical signs are the result of the combination of a gene for a mild 21-OH defect (linked to the “b” haplotype) with the gene for the severe 21-OH defect (linked to “a” and “c” haplotype).

Two siblings (SG,SF) with ambiguous external genitalia at birth were reared as a female and a male respectively. In both patients the presence of ovotestis was histologically proved, and mammary glands developed at puberty. Karyotype was 46XX in all examined cells. SF's mammary glands were surgically removed and histologically revealed the picture of male glands with enlarged ducts as observed in gynecomastia. H-Y antigen was determined by prof. U.Wolf in Freiburg, by the cytotoxicity test, using rats of the highly isogenic Lewis strain:both patients were H-Y positive. Their mother was H-Y negative,indicating an autosomal dominant mode of inheritance transmitted by the father. The varying expression of the mutation may be dependent on the degree with which the H-Y structural gene is repressed or the function of the H-Y antigen is modified by other genes. The alternative formation of an ovotestis or a testis in XX individuals (XX male syndrome and true hermaphroditism) is therefore expected to be a variation of the same pathological condition.