Biomedical subjects

T Pasqualini

Publications and source records attributed to T Pasqualini.

At least 19 recordsLinked to original sources

PubMed2004

Evaluation of catch-up growth after liver transplantation in children with biliary atresia.

Orthotopic liver transplantation (Tx) has improved survival in infants with extrahepatic biliary atresia (BA) when portoenteroanastomosis fails. Symptoms leading to Tx include liver failure, poor quality of life and growth failure. The objective of the study was to determine catch-up growth in children with BA. Medical records and growth data of 36 patients (24 girls) who received a Tx due to BA were analyzed. Thirty-two patients completed 3 yr and 15 patients 7 yr of follow-up after Tx. At Tx, the median age was 2.7 yr (range 0.7-12.6) and mean height Z score (+/-s.d.) was -1.56 (+/-1.3). Patients were divided in two groups according to age at Tx: group I (n = 10), younger than 1.0 yr, and group II (n = 26) older than 1.0 yr. Median age (range) at Tx in group I was 0.8 yr (0.7-1.0) and in group II it was 3.35 yr (1.25-12.6). Thirteen patients (nine in group I) were receptors of living related donors. We evaluated linear growth, liver and renal function, immunosuppressive regimen and allograft rejection episodes. We did not find any significant differences in allograft or renal function, immunosuppressive therapy and number of acute rejection episodes or height Z score at Tx, second and third year post-Tx between both groups. The mean height Z score at Tx in group I was -1.61 and in group II -1.54; at the second year, group I -0.66 and group II -1.08; at the third year, group I -0.17 and group II -0.85; and at the seventh year (total group) -0.3. However, the height gain at the third year was better in group I than in group II (p < 0.01, t-test). Height Z score at the third year improved more than 1 SDS in seven out of eight patients in group I and in only nine out of 24 in group II (odds ratio 11.6). We also found a correlation between height gain at the third year and age at Tx (r-0.65) and between height gain at the third year and height Z score at Tx (r-0.54) (Pearson, p < 0.05). Children with BA who are transplanted before 12 months of age presented better catch-up growth without change survival and morbidity. Orthotopic liver Tx improves survival and also enables height gain in these children.

Biliary Atresia↗

PubMed2000

Differences in anthropometric parameters and the IFG-I-IGFBP3 axis between liver and renal transplant children.

BACKGROUND: Growth can be differently altered after liver and renal transplantation (Tx) in childhood. METHODS: We compared graft function, linear growth, immunosuppression and serum IGF-I (RIA) and IGFBP3 (IRMA) concentrations in 15 liver (5.6+/-1.1 years old) and 17 renal (7.4+/-0.1 years old) Tx patients who were followed for 4-6 years. RESULTS: Graft function was normal post-liver Tx, although in renal recipients creatinine clearance decreased significantly during follow-up. Liver Tx children presented an increase in mean height of 0.92+/-0.2 SDS (P<0.01) beyond the 2nd year post-Tx, although in renal Tx patients height SDS did not improve. Immunosuppressive corticoid dosage could be decreased and discontinued in liver Tx patients, while in renal recipients it was maintained between 0.18+/-0.01 and 0.16+/-0.02 mg/kg/day. At 3.7+/-0.4 years post Tx, liver Tx patients presented higher mean serum IGF-I level, lower mean serum IGFBP3 value, leading to a higher mean IGF-I/IGFBP3 molar ratio, P<0.001. CONCLUSIONS: We found that while catch up growth coud be achieved after liver Tx, height SDS did not improve after renal Tx. This may be related to a reduced renal graft function and/or to differences in immunosuppressive corticoid dosage. In children with renal transplants a challenge for the future will reside in making it possible to substitute steroid therapy without altering graft function.

Adolescent↗

PubMed2000

Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group.

Kidney function, growth velocity, weight/height ratio, body composition, lipid profile, and bone mass were studied in a randomized, multicenter trial of deflazacort versus methylprednisone in 27 prepubertal patients with kidney transplantation. Methylprednisone (0.20+/-0.03) was replaced by deflazacort (13 patients, 0.30+/-0.03 mg/kg per day). After 12 months, creatinine clearance decreased significantly only during methylprednisone therapy. Growth velocity increased only in patients treated with deflazacort from 3.3+/-0.6 to 5.6+/-0.5 cm/year. Serum levels of several components of the insulin-like growth factor axis did not change. Weight/height ratio was increased in methylprednisone-treated patients (P<0.05) and decreased in deflazacort-treated patients (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and serum leptin increased only in methylprednisone-treated patients (P<0.025). Total cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone-treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein-cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11% (P<0.005) in deflazacort-treated patients. Total skeleton and lumbar spine bone mineral density decreased in both groups, but at 1 year methylprednisone-treated patients had lost 50% more bone. Bone mineral content decreased only in methylprednisone-treated patients (P<0.01). Our data suggest that substituting deflazacort for maintenance methylprednisone might prevent height loss, excessive bone loss, and fat accumulation; and leads to an improvement in the lipoproteins of these children.

Body Composition↗

PubMed2000

Association of Turner's syndrome and Swyer's syndrome in the same family.

We report two phenotypically and genetically different diseases in the same family. One patient presented with Turner phenotype as a result of chromosomal mosaicism 45,X/46,X, inv(X)(q21;q24) (30%/70%). Her father's sister showed 46,XY female gonadal dysgenesis (Swyer's syndrome) as a result of a point mutation in the SRY gene on her Y chromosome. DNA sequencing revealed a G-->C transversion (nucleotide position 693) resulting in a change from glycine95 to arginine (G95R). Here we report for the first time an association of Turner's syndrome and Swyer's syndrome in the same family.

Adult↗

PubMed1998

Effect of therapy with deflazacort on dyslipoproteinemia after pediatric renal transplantation.

Deflazacort is an oxazolone compound derived from prednisolone, with similar immunosuppressive action but fewer side effects. Kidney function, weight/height ratio, serum triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were studied before and 6 months after substitution of deflazacort (mean +/- SEM, 0.3 +/- 0.1 mg/kg per day) for methylprednisone (0.2 +/- 0.1 mg/kg per day) in 14 patients treated with cyclosporine, aged 3.1 to 20.3 years, 3 years after renal transplantation. Serum creatinine and calculated creatinine clearance did not change significantly, and weight/height ratio decreased from 20.0% +/- 7.1% to 12.5% +/- 6.5% (P < .005) during deflazacort therapy. Total cholesterol was reduced by 15.9% (from 233 +/- 15 mg/dL to 196 +/- 13 mg/dL, P < .01), LDL cholesterol by 25.5% (from 153 +/- 14 mg/dL to 114 +/- 12 mg/dL, P < .01), and TC/HDL cholesterol ratio by 28.3% (from 5.3 +/- 0.4 to 3.8 +/- 0.4, P < .01), whereas HDL cholesterol increased 18% (from 45 +/- 2 mg/dL to 53 +/- 2 mg/dL) and apolipoprotein A by 8.3% (from 122 +/- 5 mg/dL to 132 +/- 5 mg/dL, P < .05) during deflazacort therapy. Our data suggest that substituting deflazacort for maintenance methylprednisone therapy leads to an improvement in the lipoprotein profile of children after renal transplantation.

Adolescent↗

PubMed1998

[Growth hormone treatment before and after renal transplantation].

UNLABELLED: Children with chronic renal disease may improve height with growth hormone (GH) treatment. We studied 2 groups of children with height below 1.8 SDS and/or height velocity (HV) below the 3rd centile: 1) 6 patients with end stage renal disease (ESRD) on dialysis, aged 12.2 +/- 4.4 years (x +/- sd), with bone age of 6.8 +/- 3.3 years, 3 with Tanner stage I and 3 Tanner II; and 2) 6 children with functioning renal transplants, aged 15.5 +/- 2.5 years, with bone age 10.0 +/- 2.3 years, Tanner II-IV. Maintenance dosage of orally administered methylprednisone (MP) was 0.16 +/- 0.04 mg/kg/day. 1) Children with ESRD received GH during 1 to 3.5 years. Height SDS and HV (x +/- sd) were: pre GH -3.8 +/- 0.6 SDS and 2.6 +/- 1.4 cm/y; at 1 year of GH therapy (n = 6) -3.9 +/- 0.4 SDS and 5.1 +/- 3.2 cm/y; at 2 years (n = 5) -4.2 +/- 0.5 SDS and 3.1 +/- 0.7 cm/y; at 3 years (n = 4) -4.1 +/- 0.7 SDS and 3.3 +/- 1.5 cm/y. Height SDS and HV were: pre GH -3.0 +/- 1.9 SDS and 3 +/- 1 cm/y; at 1 year -2.5 +/- 1.5 SDS (p < 0.05) (t paired test) and 6.9 +/- 2.3 cm/y (p < 0.01). Height SDS and HV increased; creatinine clearance remained stable; there was correlation between height SDS and serum creatinine r = -0.81, creatinine clearance and HV r = 0.92, MP dose and HV r = -0.85. Five of 6 patients reached adult height of -2.8 +/- 1.3 SDS, below their target height of -0,3 +/- 0.7 SDS (p < 0.005). CONCLUSION: In patients with ESRD, GH therapy did not improve significantly height SDS and HV. In pubertal transplanted patients height SDS and HV improved and renal function remained stable; final height remained below expected genetic height. Prolonged periods of GH therapy are necessary to evaluate if final height can be improved with GH.

Adolescent↗

PubMed1997

Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation.

Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1-20 years. Methylprednisone (mean +/- SEM 0.17 +/- 0.01 mg/kg per day) was replaced by deflazacort (0.29 +/- 0.01 mg/kg per day) for a period of 1-5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6 +/- 0.5 cm/year to 5.2 +/- 0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein-3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.

Adolescent↗

PubMed1996

Hypothalamic-pituitary thyroid abnormalities in children after renal transplantation.

Patients with a successful renal transplant may have abnormalities in thyroid function. We evaluated serum thyroid hormone levels, serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), and the circadian pattern of serum TSH in 18 children aged 6.6-19.4 years (median 12.6 years), 4.0 +/- 2.9 years after renal transplantation. In 14 children, immunosuppressive therapy included methylprednisone [mean (+/-SD) 0.17 +/- 0.05 mg/ kg per day], while in 11 it included deflazacort (0.32 +/- 0.1 mg/kg per day). Seven children were studied twice, under methylprednisone and again while on deflazacort therapy. Mean total and free thyroxine (T4) values were significantly below the mean control levels (total T4 108.5 +/- 21.5 vs. 118.7 +/- 22.1 nmol/l, P < 0.05 and free T4 14.4 +/- 4.0 vs. 18 +/- 4.9 pmol/l, P < 0.001). Morning basal TSH levels were within the normal range. The mean TSH increment after TRH was 4.4 +/- 3.5 mU/l, significantly lower than that of controls (10.8 +/- 4.26, P < 0.001). Of 7 patients on methylprednisone, 4 had nocturnal TSH surges below the normal range (95% confidence limits 47%-300%); this occurred in 3 of 8 patients on deflazacort therapy. The TSH response to TRH was correlated with deflazacort dose. Patients on methylprednisone and deflazacort therapy had similar thyroid alterations. Our findings support the hypothesis that after renal transplantation some children have hypothalamic-pituitary thyroid abnormalities in which glucocorticoids may play a significant role.

Adolescent↗

PubMed1996

[Hypothalamic-pituitary-gonadal damage in adolescents with varicocele].

The incidence of varicocele in adolescent males has been reported to range from 6% to 19%. Our objective was to evaluate if there was any correlation between either varicocele grade or testicular volume and gonadotropin responses to gonadotropin-releasing hormone (LHRH) in 55 adolescents with grade (G) 2 and 3 varicocele, mean age 14.0 years (range: 10-16.8), Tanner stage I, n: 2; II, n: 9; III, n: 15; IV, n: 22; V, n:7. Testicular volume was assessed with Prader orchidometer. Basal and post LHRH serum gonadotropins were determined by radioimmunoassay. Varicocele grades were 2, n: 9; 3, n: 40; bilateral, n: 6. In patients with Tanner stage IV-V, there was a significant correlation between varicocele grade and LH area under the curve post LHRH, r: 0.45. Ipsilateral testicular growth arrest was present in 33 patients (60%) and mean left testicular volume was 77.4 +/- 9.6% (mean +/- SD) when compared to right testicular volume. LH response to LHRH was higher (p < 0.05) in those patients with left testicular volume less than 80%. In conclusion, the finding of higher LH response to LHRH in our patients with more severe ipsilateral testicular growth arrest suggests early Leydig cell dysfunction; both factors can be potential predictors of surgical indication.

Adolescent↗

PubMed1996

Growth acceleration in children with chronic renal failure treated with growth-hormone-releasing hormone (GHRH).

Growth retardation is a prominent clinical manifestation in children with chronic renal failure (CRF). Nine children with CRF (3 on conservative treatment; 3 on dialysis and 3 after renal transplantation) aged 1.6 to 14.0 (x +/- SE: 8.1 +/- 1.4) years, were treated with twice daily subcutaneous injections of 26 +/- 2.4 micrograms/kg/day growth-hormone-releasing-hormone [GHRH (1-29) NH2 Serono (Geref)] during 3 to 6 months. Mean serum urea and creatinine remained stable, although 2 patients on conservative treatment showed a moderate increase in serum creatinine. At the start of the study, height SDS was -2.2 +/- 0.2 (x +/- SE), growth velocity was 4.5 +/- 1.0 cm/year (-2.3 +/- 0.6 DS for chronological age) and growth hormone (GH) response to acute GHRH test (1 microgram/kg IV) was 62 +/- 17.5 ng/ml. Five patients increased height velocity from 3.8 +/- 0.7 to 8.0 +/- 1.2 cm/year (paired t test, p < 0.05). The peak GH response to GHRH was significantly higher in the group of growth non-responders than in the responders (p < 0.05). In conclusion, 5 out of 9 short children with CRF, 3 on conservative treatment, 1 on dialysis and 1 post renal transplantation, showed improved growth in response to GHRH therapy. No consistent effect on renal function was detected. GHRH may be an alternative therapy to increase growth velocity in patients with CRF.

Adolescent↗

PubMed1995

Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.

Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.

Animals↗

PubMed1995

Peptide and protein antigens require distinct antigen-presenting cell subsets for the priming of CD4+ T cells.

Priming of naive CD4+ T cells to Ag requires an antigen-presenting cell (APC) that can take up the Ag and present peptide bound to MHC class II molecules. We have used both in vivo and in vitro approaches to demonstrate that the APC used to prime naive CD4+ T cells depends on the initial form in which an Ag is administered. Although Ag delivered as a peptide was presented most efficiently to CD4+ T cells by DC, these APC were poor at priming to a protein form of the same Ag. In contrast, the presence of B cells was a requisite for priming to protein Ag.

Animals↗

PubMed1995

[Pseudohypoparathyroidism].

A 5 year old boy with normal phenotype and normal renal function presented tetany. Hypocalcemia and hyperphosphatemia, with increased serum levels of parathyroid hormone (PTH) were detected in serial measurements. Pseudohypoparathyroidism was diagnosed. This disease presents the biochemical abnormalities of hypoparathyroidism (hypocalcemia, hyperphosphatemia) with peripheral resistance to PTH activity. The patient was treated effectively with calcium and vitamin D supplements. The causes of hypocalcemia related to parathyroid gland activity are reviewed and the physiopathology of pseudohypoparathyroidism is described.

Alkaline Phosphatase↗

PubMed1994

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4+ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4+ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from alpha beta T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4+ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-gamma.

Animals↗

PubMed1993

Role of dendritic cells in the priming of CD4+ T lymphocytes to peptide antigen in vivo.

The contribution of dendritic cells (DC) in the initial priming of CD4+ T lymphocytes in vivo was examined. To assess the capacity of different APC to prime CD4+ T cells, a series of MHC class II I-E transgenic mice that differentially express I-E on APC were utilized. Transgenic mice that express I-E primarily on DC, on macrophages, and on B cells were primed with an I-E restricted peptide in vivo, and the extent of priming was determined by restimulation of CD4+ T cells in vitro with the same Ag. The results indicate that DC are required for priming of CD4+ T cells, and that the extent of priming correlates with the frequency of I-E+ DC. Moreover, DC alone can serve as APC for the peptide Ag, in that priming can be restored in an I-E negative mouse by the transfer of peptide-pulsed I-E+ DC. The potency of DC, compared with B cells and macrophages, to prime naive CD4+ T cells was confirmed with in vitro studies.

Animals↗

PubMed1993

Functional CD4 T cell subset interplay in an intact immune system.

Immunization with human collagen IV has been shown to lead to the selective activation of Th-1 and Th-2-like cells in vivo depending on the I-A genotype of the mice. Mice expressing I-As generate Th-1 cells, and mice expressing I-Ab generate Th-2 cells after immunization. We examined the response of (bxs)F1 hybrid mice to determine the types of CD4 T cell activated. We found that Th-1-like responses dominated, in that CD4 T cells from human collagen IV-primed mice displayed good proliferative responses and little ability to induce antibody formation, and secreted IFN-gamma and not IL-5. Most of the Th-1-like activity of F1 hybrid T cells was I-As restricted. Inhibition of Th-1 cell priming using anti-I-As antibody administered with the priming Ag in vivo revealed Th-2-like activity, in that the CD4 T cells now secreted IL-5 and not IFN-gamma and induced antibody formation. Additional studies indicated that anti-IFN-gamma treatment in vivo also revealed Th-2 cells, suggesting that I-As-restricted CD4 T cells producing or controlling the production of IFN-gamma suppress Th-2 priming.

Animals↗

PubMed1993

Therapy with a new glucocorticoid: effect of deflazacort on linear growth and growth hormone secretion in renal transplantation.

In children who have undergone successful renal transplantation, the failure of linear growth, a cushingoid appearance and obesity decrease self-esteem and hamper rehabilitation. Changes in kidney function, growth velocity, weight to height ratio and growth hormone (GH) secretion were studied before, and 2 years after, replacement of methylprednisone (6 +/- 0.3 mg/day; mean +/- SEM) by deflazacort (9.6 +/- 0.5 mg/day) 4 years after renal transplantation in 10 patients aged 9-16 years with stable renal function. Serum creatinine and creatinine clearance did not change significantly during deflazacort treatment. In 8 patients at Tanner stage I, growth velocity increased significantly during the 1st and 2nd year of deflazacort therapy (p < 0.01 and p < 0.005, respectively). Weight to height ratio decreased significantly during the 1st and 2nd year of deflazacort treatment (p < 0.005, p < 0.02, respectively) though in 3 patients, this returned to base levels after 2 years of deflazacort therapy. The mean spontaneous GH secretion increased significantly (p < 0.05). There was a correlation between growth velocity and spontaneous GH secretion during deflazacort therapy. The cushingoid appearance decreased in the majority of patients. Renal function remained stable.

Adolescent↗

PubMed1992

Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation.

Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

Body Height↗