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Biomedical subjects

A Conti

Publications and source records attributed to A Conti.

At least 73 records · Page 4Linked to original sources
PubMed1997

Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone.

OBJECTIVE: Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone. MATERIAL AND METHODS: The study including 14 consecutive metastatic prostate cancer patients with poor clinical conditions (median age: 70.5 years; median PS: 50%), refractory or resistant to a previous therapy with the LHRH analogue triptorelin alone. Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in the evening every day until progression, starting 7 days prior to triptorelin. RESULTS AND CONCLUSIONS: A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 patients with persistent thrombocytopenia prior to study. Mean serum levels of both PRL and IGF-1 significantly decreased on therapy. Finally, a survival longer than 1 year was achieved in 9/14 (64%) patients. This preliminary study would suggest that the concomitant administration of the pineal hormone MLT may overcome the clinical resistance to LHRH analogues and improve the clinical conditions in metastatic prostatic cancer patients.

Administration, Oral↗
PubMed1997

Absence in human milk of bovine beta-lactoglobulin ingested by the mother. Unreliability of ELISA measurements.

OBJECTIVES: To analyze the presence of bovine beta-LG in breast milk. METHODS: Human milk samples from 14 healthy non-atopic women on diets with different cow's milk contents were examined. The total concentration of beta-LG immuno-like proteins (beta-LGIP) was determined by enzyme linked immunosorbent assay (ELISA). Identification of antigens was done by N-terminal sequencing. RESULTS: beta-LGIP reactivity of the milk from subjects on different diets was not significantly different. Human lactoferrin, beta-casein and alpha-lactalbumin, were identified as cross-reacting antigens. CONCLUSIONS: False-positive results in ELISA determinations of bovine beta-LG in human milk might be due to cross-reactions between polyclonal antibodies and different protein antigens.

Animals↗
PubMed1997

Macrocystic serous cystadenoma of the pancreas. Diagnostic, therapeutic and pathological considerations of three cases.

BACKGROUND: Macrocystic serous cystadenoma (MSC) of the pancreas is a new entity that has recently been well recognised. This tumour is quite similar in aspect to the mucinous cystic tumours (MCT) but its prognosis is much better, so that a correct diagnosis before surgery is important. PATIENTS: Three patients undergoing surgery in the 1st Surgical Clinic of the University of Bologna for suspected cystic lesions were found to have macrocystic serous cystadenoma (MSC) of the pancreas. In two cases a biopsy was performed during surgery, but in only one was a correct diagnosis of MSC made; in the other the diagnosis was lymphangioma. In the remaining case a biopsy was not performed because the high 19/9 CA level in the blood suggested a diagnosis of MCT of the pancreas. In all 3 cases the tumour was successfully removed by surgery. CONCLUSIONS: Macrocystic serous cystadenoma (MSC) of the pancreas represents a variant of the serous cystic tumors, which encompass microcystic adenoma and serous cystadenocarcinoma. MSC must be distinguished from MCT because it exhibits a different biological pattern and requires a different surgical approach. Therefore, we would underline the importance of a biopsy in making the differential diagnosis.

Adult↗
PubMed1996

Amino acid sequence and crystal structure of buffalo alpha-lactalbumin.

Isolation, purification, amino acid sequence determination and X-ray crystal structure of buffalo alpha-lactalbumin were performed in order to gain further knowledge of the molecular basis of alpha-lactalbumin in the lactose synthase complex. The deduced amino acid sequence differs at one position from the bovine alpha-lactalbumin sequence (at position 17). The refined crystal structure at 2.3 A is very similar to those previously reported for human and baboon alpha-lactalbumins. However, a portion of the molecule (residues 105-109) exhibits different conformation. It forms a 'flexible loop', and appears to be a functionally important region in forming the lactose synthase complex.

Amino Acid Sequence↗
PubMed1996

Screening for mutations in exon 11 of the BRCA1 gene in 70 Italian breast and ovarian cancer patients by protein truncation test.

The most common mutations in the familial breast and ovarian cancer susceptibility gene BRCA1 are frameshift and nonsense mutations, which lead to the synthesis of truncated proteins. On this ground, we have analysed BRCA1 exon 11, which includes about 61% of coding region, in germline DNA from 70 Italian breast and/or ovarian cancer patients, using the protein truncation test (PTT). BRCA1 mutations were identified in nine of 29 (approximately 31%) patients with a family history of cancer and in three of 41 (approximately 7%) women with early-onset breast carcinomas, and were subsequently characterized by sequence analysis. In addition, BRCA1 mutations were also detected in six affected relatives of two positive index cases. The observed frequencies of mutations were not significantly different from those expected on the basis of the phenotypic characteristics of patients and their families, indicating that PTT is a rapid and sensitive method that can be used for a first BRCA1 mutational screening. The histological findings in BRCA1 mutated cases showed that eight of nine (approximately 89%) breast carcinomas were of grade III and nine of 9 (100%) ovarian carcinomas were of the endometrioid type (eight of grade III and one of grade II). This suggests that specific histological characteristics may represent additional criteria for selection of cases eligible to BRCA1 mutational analysis.

Adult↗
PubMed1996

Differential distribution of ryanodine receptor type 3 (RyR3) gene product in mammalian skeletal muscles.

Activation of intracellular Ca(2+)-release channels/ryanodine receptors (RyRs) is a fundamental step in the regulation of muscle contraction. In mammalian skeletal muscle, Ca(2+)-release channels containing the type 1 isoform of RyR (RyR1) open to release Ca2+ from the sarcoplasmic reticulum (SR) upon stimulation by the voltage-activated dihydropyridine receptor on the T-tubule/plasma membrane. In addition to RyR1, low levels of the mRNA of the RyR3 isoform have been recently detected in mammalian skeletal muscles. Here we report data on the distribution of the RyR3 gene product in mammalian skeletal muscles. Western-blot analysis of SR of individual muscles indicated that, at variance with the even distribution of the RyR1 isoform, the RyR3 content varies among different muscles, with relatively higher amounts being detected in diaphragm and soleus, and lower levels in abdominal muscles and tibialis anterior. In these muscles RyR3 was localized in the terminal cisternae of the SR. No detectable levels of RyR3 were observed in the extensor digitorum longus. Preferential high content of RyR3 in the diaphragm muscle was observed in several mammalian species. In situ hybridization analysis demonstrated that RyR3 transcripts are not restricted to a specific subset of skeletal-muscle fibres. Differential utilization of the RyR3 isoform in skeletal muscle may be relevant to the modulation of Ca2+ release with respect to specific muscle-contraction properties.

Animals↗
PubMed1996

Alpha and beta isoforms of ryanodine receptor from chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3.

To define the relationship between the two ryanodine receptor (RyR) isoforms present in chicken skeletal muscle, we cloned two groups of cDNAs encoding the chicken homologues of mammalian RyR1 and RyR3. Equivalent amounts of the two chicken isoform mRNAs were detected in thigh and pectoral skeletal muscles. RyR1 and RyR3 mRNAs were co-expressed in testis and cerebellum whereas RyR3 mRNA was expressed also in the cerebrum and heart. The full-length sequence of the chicken RyR3 cDNA was established. The RyR3 receptor from chicken had the same general structure as mammalian and amphibian RyRs. The 15089 nt cDNA encoded a 4869-amino-acid-long protein with a molecular mass of 552445. The predicted amino acid sequence of the chicken RyR3 showed 86.9% identity to mammalian RyR3 and 85.6% to frog RyR3. Antibodies specific for chicken RyR1 and RyR3 recognized two different proteins with an apparent molecular mass of about 500 kDa. The two proteins differ slightly in their apparent molecular mass on SDS/PAGE: the protein recognized by antibodies against RyR3 had a higher mobility than the protein recognized by the antiserum against RyR1. Antibodies against RyR1 detected a protein already present in chicken skeletal muscle from 12-day-old embryos and older, while antibodies against RyR3 isoform detected a protein in muscle from only 18-day-old embryos and older. The expression patterns of RyR1 and RyR3 superimpose with those previously reported for the alpha and beta isoforms respectively. We conclude that alpha and beta isoforms present in chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3.

Amino Acid Sequence↗
PubMed1996

Effects of recombinant growth hormone (GH) treatment on bone mineral density and body composition in adults with childhood onset growth hormone deficiency.

Lumbar spine, whole proximal femur and total body bone mineral density (BMD, g/cm2) and the regional soft tissue composition were measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) in eight adults with childhood onset GHD, before and after 6 months of recombinant GH treatment (0.5 IU/kg/week). Data obtained from patients were compared with those recorded in an age and sex matched control group. Before treatment, lumbar (L2-L4) spine BMD (mean +/- SD: 0.811 +/- 0.159 g/cm2), whole proximal femur BMD (0.739 +/- 0.094 g/cm2) and total body BMD (0.946 +/- 0.087 g/cm2) of patients were significantly (p < 0.001, 0.01 and 0.001, respectively) lower than those recorded in an age- and sex-matched control group (1.077 +/- 0.155 g/cm2, 0.968 +/- 0.166 g/cm2 and 1.168 +/- 0.058 g/cm2, respectively), although three patients showed BMD values at the lower limit of the normal range. Mean lumbar spine BMD, whole proximal femur BMD and total body BMD did not significantly change alter 6 months' GH treatment (-1.4 +/- 3.7%, +2.7 +/- 3.7% and -1.1 +/- 5.0% vs basal values, respectively). On the other hand, trochanteric subregion showed a significant 4.8 +/- 5.3% increase (vs basal, p < 0.05), while other hip subregions did not show significant changes. GH therapy caused marked effects on body composition; in fact, a significant decrease (p < 0.01) of trunk fat (-25.2 +/- 15.0%) and a marked increase (p < 0.01) of limbs lean mass (+10.0 +/- 5.3%), resulting in a significant (p < 0.02) reduction (-16.5 +/- 13.5%) of the axial to peripheral fat ratio (APFR), were clearly evident after six months of therapy. In conclusion, our study shows that six months of GH treatment do not exert relevant effects on the BMD of adults with childhood onset GHD. On the contrary, the effects of GH therapy on body composition are more marked, being clearly appreciable after six months of treatment.

Adult↗
PubMed1996

Modifications of biochemical markers of bone and collagen turnover during corticosteroid therapy.

Serum bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and aminoterminal propeptide of type III procollagen (PIIINP) levels were determined in 8 patients with autoimmune disorders (2 with systemic lupus erythematosus, 3 with rheumatoid arthritis, 2 with Sjögren's syndrome and 1 with mixed connective tissue disease) before and after 1, 2 and 4 months of treatment with oral prednisone (at a dosage of 1 mg/kg bw/day, p.o. during the first month, then reduced to 0.1-0.2 mg/kg bw/day). Before treatment mean serum BGP (mean +/- SE: 5.3 +/- 0.4 ng/ml) and ICTP (2.8 +/- 0.2 ng/ml) levels were similar to those recorded in an age and sex matched control group (n = 40: 5.4 +/- 0.1 ng/ml and 4.1 +/- 0.3 ng/ml, respectively). On the other hand, serum PIIINP levels (2.2 +/- 0.3 ng/ml) were significantly (p < 0.008) lower than those found in controls (3.3 +/- 0.2 ng/ml). During glucocorticoid therapy, serum BGP levels significantly decreased after 1 month (2.9 +/- 0.4 ng/ml; P < 0.001), but returned to baseline values after 2 and 4 months of treatment (4.7 +/- 0.4 ng/ml and 5.3 +/- 0.3 ng/ml, respectively). On the contrary, no significant changes were observed in serum ICTP levels during treatment (1st month: 2.7 +/- 0.4 ng/ml; 2nd month: 3.0 +/- 0.4 ng/ml; 4th month: 2.4 +/- 0.3 ng/ml). Serum PIIINP mean concentration significantly decreased after 1 (1.6 +/- 0.3 ng/ml; P < 0.004) and 2 months of glucocorticoid administration (1.5 +/- 0.2 ng/ml; P < 0.01); after 4 months, serum PIIINP levels were again reduced as before therapy (1.8 +/- 0.2 ng/ml). In conclusion, our study shows the presence of normal bone turnover indexes and of altered collagen synthesis in patients with autoimmune disorders. The use of high doses of oral steroids is associated with a prompt decrease of bone formation and collagen synthesis, without any significant changes in bone resorption; however, the negative effects on bone formation and collagen synthesis seem to revert after lowering corticosteroid dosage. Serial determinations of the markers of bone and collagen turnover are able to give useful and reliable information on the peripheral effects of steroids excess.

Adult↗
PubMed1996

Sensitization to reactive textile dyes in patients with contact dermatitis.

Reactive dyes are used especially for colouring natural fibres (cotton, silk and wool) that are widely used in Western countries, particularly Italy, in the production of clothes. The aim of our study was to investigate sensitization to the most commonly used reactive textile dyes in patients undergoing patch tests, and to assess the clinical relevance of contact sensitization to these dyes. 1813 consecutive patients underwent patch tests with the GIRDCA standard series and an additional textile series of 12 reactive dyes. 18 of these patients were sensitized to reactive dyes (0.99%) (4 only to reactive dyes). The dyes most frequently responsible for positive patch tests were Red Cibacron CR and Violet Remazol 5R (respectively, 8 and 5 positivities). In 5 cases only was a history of intolerance to particular garments given; of 4 patch tests performed with pieces of garment, 2 were positive. In 1 occupationally-exposed patient, airborne contact dermatitis was suspected. Owing to the lack of up-to-date patch test series, some cases of allergic contact dermatitis from textile dyes are probably misdiagnosed: new colouring agents are continuously introduced to the market, so that a close relationship with textile industry is necessary to improve our diagnostic tools.

Adolescent↗
PubMed1996

HPLC validation of a circadian melatonin rhythm in the pineal gland of inbred mice.

Production of melatonin in the pineal gland of inbred mice such as C57B1/6J, BALB/c and AKR strains is still a matter of debate. In previous studies, we and other authors showed that these strains of inbred mice have a clear-cut circadian rhythm of serum melatonin and urinary 6-hydroxy-melatonin-sulphate. In contrast, other groups claimed these mice are unable to synthesize melatonin. These studies were based on RIA measurements and/or estimates of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities. In the present study we validate the presence of melatonin in the pineal gland of C57B1/6, BALB/c, and AKR mice by HPLC determinations. We found a short-term melatonin peak in the middle of the dark period with a pattern which mirrors that found previously in the serum. The possibility remains, although it seems unlikely, that the pineal melatonin rhythm measured here represents melatonin produced elsewhere which then was subsequently taken up by the pineal gland.

Animals↗
PubMed1996

Role of the pineal gland and melatonin in the development of autoimmune diabetes in non-obese diabetic mice.

Earlier studies on the immunoregulatory role of the pineal gland and melatonin revealed that melatonin counteracts immunosuppression and thymus atrophy induced by stress or corticosteroid treatment. Moreover, melatonin protects mice injected with encephalitogenic viruses, synergizes with interleukin-2 (IL-2) in cancer immunotherapy and rescues hematopoiesis from cancer chemotherapy toxicity. In regard to the mechanism of action, melatonin seems to act directly on CD4+ lymphocytes which release opioid peptides with immunoenhancing properties along with other cytokines. Because of these findings, we investigated the role of the pineal gland and melatonin in autoimmune diabetes mellitus type I using, as an experimental model, female non-obese diabetic (NOD) mice. Mice were pinealectomized or treated chronically with melatonin (injected subcutaneously or administered via drinking water). This paper shows that neonatal pinealectomy accelerates the development of the disease in female NOD mice while exogenous melatonin protects the animals. This in spite of the fact that melatonin increased the production of insulin autoantibodies (IAA). We conclude that the pineal gland and melatonin influence the development of autoimmune diabetes although the mechanism of action that needs further investigation.

Animals↗
PubMed1996

Melatonin-induced T-helper cell hematopoietic cytokines resembling both interleukin-4 and dynorphin.

We have reported that melatonin exerts colony stimulating activity and rescues bone marrow cells from apoptosis induced either in vivo or in vitro by cancer chemotherapy compounds. We proposed that melatonin regulates interleukin-4 (IL-4) production in bone marrow T-helper cells and that IL-4 stimulates adherent stromal cells to produce colony stimulating factors (CSF). However, in further investigations we did not find any direct evidence of the ability of melatonin to stimulate IL4. We found that besides anti-IL4 monoclonal antibody (mAb), the opioid antagonist naltrexone also neutralized the colony stimulating activity and part of the hematopoietic protection exerted by melatonin. SDS-PAGE and immunoblotting analysis of supernatants of bone marrow T-helper cells incubated overnight with melatonin revealed the presence of two proteins with an apparent molecular weight of 15 and 67 kDa, which were recognized by both anti-common opioid sequence (Tyr-Gly-Gly-Phe) and anti-IL4 mAbs. When Abs against known opioid peptides were tested, only anti-dynorphin B Ab labeled the 67 kDa but not the 15 kDa protein. These melatonin-induced-opioids (MIO) were separated by gel filtration. The lower molecular weight MIO (MIO15) seems to mediate the naltrexone-sensitive hematopoietic effects of melatonin. Consistently, we found the presence of opioid receptors in adherent bone marrow cells. Apparently, the higher molecular weight protein, MIO67, was responsible for the naltrexone-insensitive part of the melatonin-induced hematopoietic rescue. These melatonin-induced T-helper cell products which resemble both IL-4 and dynorphin B might represent a new family of opioid peptides with hematopoietic and immune functions.

Animals↗
PubMed1996

Human milk proteins may interfere in ELISA measurements of bovine beta-lactoglobulin in human milk.

It is widely believed that cow's milk proteins ingested by the mother, in particular beta-lactoglobulin (beta-LG), can pass into breast milk and thus sensitize predisposed infants. However, studies to evaluate bovine beta-LG in human milk have given conflicting results. The aim of this study was to analyse the correlation between the amount of cow's milk in the mother's diet and the presence of bovine beta-LG in breast milk. Human milk samples from 14 healthy non-atopic women on diets with different cow's milk contents were examined. The total concentration of bovine beta-LG or beta-LG immuno-like proteins (beta-LGIP) was determined by enzyme-linked immunosorbent assay (ELISA). Two separation procedures utilizing ELISA plates and an affinity chromatography column were set up to identify the human whey components recognized by the anti-beta-LG antibodies. beta-LGIP reactivities of milk from three groups on different diets were not significantly different. After splitting the antigen-antibody complexes, three main protein components, human lactoferrin, human beta-casein and human alpha-lactalbumin, were identified. This study would suggest that, at least in healthy subjects, false-positive results in ELISA determinations of bovine beta-LG in human milk might be due to cross-reactions between polyclonal antibodies and different protein antigens.

Adult↗
PubMed1996

Low urinary GH levels in normal statured obese children.

Urinary GH (u-GH) levels were evaluated in 240 children (age range 5-14 years; 136M, 104F) of normal height (25-90th centile); 165 children were defined as "non-obese" (body mass index (BMI) < 75th centile for their chronological age (CA)) and 75 as "obese" (BMI > 75th). U-GH levels were determined using a two-site enzyme immunometric assay and calculated as the mean obtained from the values of three consecutive first morning voidings; results were expressed as both u-GH concentration (ngl-1) and u-GH excretion (ng per night). Multiple regression analysis revealed that in all children (non-obese and obese) most of the variation in u-GH levels (ngl-1 and ng night-1) was explained by BMI (coefficient: -0.72, p < 0.0001 and coefficient: -0.10, p < 0.001, respectively) and chronological age (coefficient: 1.03, p < 0.01 and coefficient; 0.27, p < 0.001, respectively), whereas sex and pubertal stage did not add significance to the variance. In obese children, mean u-GH concentration and u-GH excretion (per night) levels were significantly lower than those recorded in non-obese children both before and during puberty. A similar trend towards higher u-GH levels at puberty was found in non-obese and obese children. In conclusion, our study shows that u-GH levels are (a) related to CA and BMI in the general population and (b) significantly lower in obese than in non-obese children, in spite of their comparable normal height. The measurement of u-GH excretion in the assessment of children with short stature needs to take into consideration the role of marked ponderal excess, which is associated "per se" with significantly lower u-GH levels.

Adolescent↗
PubMed1996

Serum bone Gla protein and carboxyterminal cross-linked telopeptide of type I collagen in patients with Cushing's syndrome.

Serum bone Gla protein, a marker of bone formation, and carboxyterminal cross-linked telopeptide of type I collagen levels, an index of bone resorption, were evaluated in eight patients with active Cushing's syndrome and in four with 'preclinical' Cushing's syndrome, before and after surgery. In basal conditions, serum bone Gla protein levels were significantly lower (p < 0.0001) in patients with active Cushing's syndrome (1.0 +/- 0.35 ng/ml) than in controls (5.4 +/- 0.15 ng/ml); two out of four patients with the 'preclinical' form had reduced bone Gla protein levels, while in the other two cases levels were in the normal range. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (3.0 +/- 0.4 ng/ml), although slightly reduced, were similar to those recorded in controls (4.1 +/- 0.3 ng ml), both in patients with active and with preclinical Cushing's syndrome. After surgery serum levels of both marker proteins significantly increased in seven out of eight patients with active Cushing's syndrome; in one patient, who was not cured after surgery, bone Gla proteins levels remained lower than in normals, while levels of carboxyterminal cross-linked telopeptide of type I collagen had a transient increase after six months. In the two patients with a 'preclinical' Cushing's syndrome who underwent surgery, a significant rise of the levels of both marker proteins was observed, similar to that observed in patients with active Cushing's syndrome. It was concluded that serial determinations of these new markers of bone formation and resorption may be usefully employed to follow-up the clinical course of Cushing's syndrome and provide information on the rate of bone turnover in response to medical and/or surgical therapies. Moreover, the evaluation of these markers in preclinical states of Cushing's syndrome might suggest the need for surgery.

Adult↗
PubMed1996

Growth, growth hormone and cognitive functions.

The interactions among short stature, growth hormone (GH) and cognitive functions have been extensively studied so far. However, although it seems well established that short stature is associated with cognitive problems, little effort has been made to point out the presence of specific psychological effects related to the different forms of short stature. In 'short normal' children, the presence of a scholastic underachievement seems to suggest that short stature 'itself' might predispose these patients to some of their psychosocial difficulties. The higher incidence of academic failure, in presence of a normal intellectual functioning, has been attributed to environmental and psychosocial factors, including over-protective parents and low self-esteem resulting from the impact of short stature. These problems appear to be common also to other forms of short stature (such as Turner's syndrome) where, however, they are frequently associated with other specific deficits. The in vivo model which might allow, at least in part, better understanding of GH (per se)-dependent effects is represented by GH deficiency (GHD), in which, however, the specific role of GH on psychological functioning is frequently masked by the presence of associated hormonal deficiencies. Children with isolated GHD are reported to have specific educational deficits, in particular learning disability and attention-deficit disorders, which have been tentatively attributed to a compromised intellectual potential. The psychological effects of long-term GH treatment in children with GHD still remain controversial, with some retrospective studies describing a generally beneficial outcome. Since early experiences in school are closely related to success in adult life, the possible implications that GHD during childhood holds during adulthood have been recently considered. Although regional differences have been observed in subgroups of adults with GHD, it seems that these patients have normal cognitive functions and educational attainment, but are more likely to be unemployed (and unmarried) than members of the general population. In general, patients with GHD, who have been treated at centers where psychological counselling was an integral part of the treatment program, seem to be better adjusted in adult life. For these reasons, a multidisciplinary treatment approach could allow early detection of problems in academic achievement and psychosocial development in patients with short stature, being immediately able to provide the appropriate educational and counselling interventions.

Adult↗