The mechanisms regulating the synergic effect of growth hormone and other hormones during pubertal spurt are not completely clarified. We enrolled 64 females of Caucasian origin and normal height ...including 22 prepubertal girls, 26 pubertal girls, and 16 adults to evaluate the role of Growth Hormone/Insulin-like growth factor-I axis (GH/IGF-I) during the pubertal period. In these subjects both serum IGF-I and growth hormone binding protein levels, as well as quantitative growth hormone receptor (GHR) gene expression were evaluated in peripheral lymphocytes of all individuals by real-time PCR. Our results showed significantly lower IGF-I levels in women (148±10 ng/ml) and prepubertal girls (166.34±18.85 ng/ml) compared to pubertal girls (441.95±29.42 ng/ml; p<0.0001). Serum GHBP levels were significantly higher in prepubertal (127.02±20.76 ng/ml) compared to pubertal girls (16.63±2.97 ng/ml; p=0.0001) and adult women (19.95±6.65 ng/ml; p=0.0003). We also found higher GHR gene expression levels in pubertal girls 174.73±80.22 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase) compared with other groups of subjects women: 42.52±7.66 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase); prepubertal girls: 58.45±0.18.12 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase), but the difference did not reach statistical significance. These results suggest that sexual hormones could positively influence GHR action, during the pubertal period, in a dual mode, that is, increasing GHR mRNA production and reducing GHR cleavage leading to GHBP variations.
It is a common knowledge that GH exhibits a large number of metabolic effects, involving lipid and glucose homeostasis. The aim of the study was to investigate the effect of one year GH therapy on ...metabolic parameters and adipokines in GH deficient (GHD) children. Sixteen prepubertal children (11 M and 5 F) with complete GHD (age range: 3.4-14.7 years) and 20 (13 M and 7 F) age and sex-matched healthy children (age range: 4.6-12.3 years) were studied. Blood was collected from patients before starting GH therapy (0.025 mg/kg/day) and one year later, and from healthy children to measure adiponectin, leptin, osteoprotegerin, resistin, interleukin (IL)-6, tumor necrosis factor (TNF)-α levels, and other glucose and lipid metabolism parameters. Adiponectin and resistin levels were significantly higher (49980 ng/ml vs. 14790 ng/ml and 11.0 pg/ml vs. 6.3, respectively) in GHD children before GH therapy than in controls. Serum IGF-I levels (p=0.0001) and height SDS (p<0.0001) significantly increased after 12 months' of GH therapy. There was a loss of body fat reflected by a significant decline in tricep (p=0.0003) and subscapular skinfold thickness SDS (p=0.0023). After 12 months, there was a significant rise in insulin (p=0.0052) and leptin levels (p=0.0048) and a significant decrease in resistin (p=0.0312) and TNF-α (p=0.0137). We observed that lipid and glucose metabolisms are only slightly affected in GHD children. Growth hormone replacement therapy affects some factors, such as leptin, resistin and fat mass, suggesting that also in children, GH treatment has a role in the regulation of factors secreted by adipose tissue.
Early detection of suspected poor adherence to growth hormone (GH) therapy is crucial to achieve normal final height in GH-deficient (GHD) patients.
106 children (73 M, 33 F) with a median age of ...10.47±3.48 years (mean±standard deviation score (SDS)) exhibited short stature (-1.76±0.64 SDS) and a delayed bone age (8.68±3.42 years). Severe GHD was found in 28, while partial GHD was seen in 78 cases, with low IGF-I values. Recombinant human GH was administered by daily subcutaneous injection at a dosage of 21 µg/kg in prepubertal and 25 µg/kg in pubertal patients.
Poor adherence was suspected in a number of patients, but clearly demonstrated in only 4 cases with persistent reduced height velocity in spite of a corrected therapeutic regimen. These patients admitted incomplete adherence to GH injections and clinical and anthropometric measurements revealed their poor response to therapy.
To efficaciously improve adherence in GHD patients, it is mandatory to regularly interview patients; a non-aggressive approach might be utilized to ensure effective communication with patients and their parents.
Deletions of the long arm of chromosome X in males are a rare cause of X-linked intellectual disability. Here we describe a patient with an interstitial deletion of the Xq21.1 chromosome.
In a 15 ...year boy, showing intellectual disability, short stature, hearing loss and dysmorphic facial features, a deletion at Xq21.1 was identified by array-CGH. This maternally inherited 5.8 Mb rearrangement encompasses 14 genes, including BRWD3 (involved in X-linked intellectual disability), TBX22 (a gene whose alterations have been related to the presence of cleft palate), POU3F4 (mutated in X-linked deafness) and ITM2A (a gene involved in cartilage development).
Correlation between the clinical findings and the function of gene mapping within the deleted region confirms the causative role of this microrearrangement in our patient and provides new insight into a gene possibly involved in short stature.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Laryngeal squamous cell carcinomas (LSCCs) typically have an excellent prognosis for stage I tumors but a significant risk of locoregional and distant recurrence for intermediate to ...advanced disease. This study will investigate the clinical relevance of the tumor microenvironment in a large cohort of treatment‐naïve patients affected by stage II–IV LSCC.
Methods
Whole slide‐based digital pathology analysis was applied to measure six immune cell populations identified by immunohistochemistry (IHC) staining for CD3, CD8, CD20, CD66b, CD163 and CD38. Survival analysis was performed by Cox proportional hazards models and unsupervised hierarchical clustering using the k‐means method. Double IHC staining and in‐situ hybridisation by RNAscope allowed further analysis of a protumoral B cell population.
Results
A cohort of 98 patients was enrolled and analysed. The cluster of immune‐infiltrated LSCCs demonstrated a significantly worse disease‐specific survival rate. We also discovered a new association between high CD20+ B cells and a greater risk of distant recurrence. The phenotypic analysis of infiltrating CD20+ B cells showed a naïve (BCL6−CD27−Mum1−) regulatory phenotype, producing TGFβ but not IL10, according to an active TGFβ pathway, as proved by positive pSMAD2 staining.
Conclusion
The identification of regulatory B cells in the context of LSCC, along with the activation of the TGFβ pathway, could provide the basis for new trials investigating the efficacy of already available molecules targeting the TGFβ pathway in the treatment of LSCC.
Our findings support the presence of a prometastatic population of CD20+ B cells (Breg) in the tumor microenvironment of laryngeal squamous cell carcinoma (LSCC). The detected activation of the TGFβ pathway is the basis for new trials investigating the efficacy of already available molecules targeting the TGFβ pathway in the treatment of LSCC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction
Human herpes virus 6 (HHV6) infection is a self-limiting illness occurring in early childhood. As with other herpes viruses, the encephalopathy associated with HHV6 is often attributable ...to the reactivation of a virus previously latent in human brain tissue. Previous reports on HHV6 encephalopathy dealt mainly with virus reactivation in immune-depressed older children and, above all, refer to encephalitis and not to meningoencephalitis. Complications are rare in healthy children. Encephalopathy has rarely been associated with HHV6 infection in children not affected by chronic disease.
Purpose
The aim of this study was to evaluate sequelae of HHV6 meningoencephalitis in previously healthy children.
Results
We report three cases of HHV6 meningoencephalitis in previously healthy children followed for a 10-year period. Two of the patients presented invalidating sequelae. In detail, one patient developed speech disturbance and the other persistent hemiplegia and bilateral visual deficit. To our knowledge, this is the first case in which an ocular complication developed in the course of HHV6 meningoencephalitis.
Conclusion
HHV6 meningoencephalitis can be associated with a wide range of clinical outcomes, from long-term neurological sequelae to a benign post-infectious clinical course.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and ...interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4±3.1 years), with the clinical characteristics of GHD (height: -2.3±0.5 SDS; height velocity -2.3±1.5 SDS; IGF-I -1.2±0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment.
Obesity can be defined as an excess of adipose tissue. It is associated to a significantly increased risk of cardiovascular disease, hypertension, diabetes mellitus and hypercholesterolemia. The ...results of the Italian survey called Okkio alla Salute (2010), which was attended over 42'000 students of third-class of primary school and 44'000 parents, confirm bad eating habits, sedentary lifestyles and excess weight. In particular, 22,9% of the children resulted overweight and 11,1% obese. The prevalence of obesity is higher in the south of Italy than in the north and in males rather than in females. Moreover, parents do not always have a real idea of the physical aspect of their son: 36% of the mothers of overweight or obese children are do not believe their child is overweight. Just 29% of them think that the quantity of food eaten by their child is excessive. The relative risk for an obese child to become an obese adult increases with the age and is directly correlated to the severity of overweight. Among obese children of preschool age, 26 to 41% will be an obese adult., Among scholar children, the percentage increases to 69%. The paper describes a multidisciplinary approach the disease, in fact, dietary and behavioural modifications, associated with physical activity, have the purpose of educate overweight and of preventing the onset of complications or reducing their severity if already present and reversible.
Aim
: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated.
Methods
: In 12 GH-deficient (GHD) and 12 ...bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio.
Results
: We found a significant (
p
<0.05) increase in growth velocity in both groups during the first year of GH treatment (non-GHD: from −1.7 to 5.4 SDS; GHD: from −1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28±653.15 euro) and bioinactive GH children (1639.55±631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68±2018.1 euro) and bioinactive GH children (11355.08±1747.61 euro).
Conclusion
: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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