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Biomedical subjects

M Cappa

Publications and source records attributed to M Cappa.

At least 19 recordsLinked to original sources
PubMed2002

Does Graves' disease during puberty influence adult bone mineral density?

AIM: To evaluate the bone mineral density at lumbar spine and at femoral neck in a group of young adults in whom Graves' disease developed during childhood and adolescence. PATIENTS AND METHODS: We examined 28 patients (5 male, 23 female, age 20.9 +/- 3.3 years) who were 11.8 +/- 2.9 years old at the onset of Graves' disease. They were treated either with methimazole (14 patients) or with methimazole plus l-thyroxine (14 patients). At the time of the investigation, 13 patients were considered cured following antithyroid treatment, 2 were still on antithyroid drugs, 3 were on replacement therapy with l-thyroxine because of hypothyroidism, and 10, treated either surgically or with (131)I, were on replacement therapy. The bone mineral density was measured at the lumbar spine (L2-L4) and at the femoral neck, using dual-energy X-ray absorptiometry. RESULTS: The spinal bone mineral density SD score was -0.28 +/- 1.02, the femoral neck bone mineral density SD score was 0.36 +/- 1.02, and both were not different from zero (NS). We did not find any correlation between the bone mineral density of the femoral neck and that of the lumbar spine and the clinical parameters. CONCLUSION: Graves' disease, beginning in childhood and adolescence, when appropriately treated, does not affect attainment of peak bone mass.

Absorptiometry, Photon↗
PubMed2001

Th 1 cytokine production by peripheral blood mononuclear cells in X-linked adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) are the two most frequent clinical phenotypes of the same genetic defect leading to the accumulation of very long chain fatty acids (VLCFA). Previous studies have suggested that inflammatory cytokines may play a role in the cerebral demyelination and in phenotype expression of the disease. We analyzed cytokine production by stimulated peripheral blood mononuclear cells (PBMC) from 17 patients (four asymptomatic subjects, eight AMN and five ALD). Our results show that lipopolysaccarides (LPS) stimulated PBMC from both symptomatic and asymptomatic patients have an increased production of IL-12 and TNFalpha compared to controls, while after phitoemoagglutinin (PHA) stimulation we observed a decreased production of IL-6 and IL-10. These data indicate that, following an immunological stimulus, PBMC from patients have an increased production of cytokines typical of a Th1 cell response which is able to promote the inflammatory process. This characteristic profile of cytokine production could be related to the biochemical defect and could have a role in central nervous system (CNS) pathogenesis.

Adolescent↗
PubMed2001

Unresolved problems concerning optimal therapy of puberty in children with chronic renal diseases.

Many children with chronic renal insufficiency (CRI) show growth retardation and severely delayed pubertal development. Successful renal transplantation (RTx) also rarely results in full growth rehabilitation. Pubertal height gain in CRI patients is only 58% and 48% of that observed in late-maturing boys and girls, respectively. Growth retardation in both CRI and RTx patients is not the result of abnormal GH secretion or decreased levels of IGF-I, but rather of elevated levels of IGFBPs inhibiting the bioavailability of the IGFs. In RTx patients prednisone may also inhibit growth directly via inhibition of bone matrix formation. Several studies have convincingly shown that GH therapy at a dose of 4 IU/m2/day results in a sustained improvement of growth in prepubertal and pubertal children with CRI and in growth-retarded prepubertal and pubertal post-transplant patients. The following consensus was reached concerning optimal therapy of puberty in children with chronic renal disease. GH therapy does not lead to an earlier start of puberty. It is safe to give GH to RTx patients if transplant function is stable. GH therapy will not accelerate bone maturation and can improve the final height of children with CRI and after RTx. Increasing the GH dose above 4 IU/m2/day in pubertal RTx patients does not increase height gain or final height and is not advised as it may increase insulin resistance. GH should best be started before the start of the pubertal growth spurt but will still be effective in RTx patients with advanced bone age. GH testing should not be a prerequisite for starting GH therapy. It is important to optimise other therapies during puberty. During GH therapy of RTx patients use minimum daily, not alternate-day, steroid dosing. Further research is still required on the possible long-term effects of GH therapy in children with chronic diseases. Two studies demonstrated improved long-term growth and final height within the target height range, without significant side effects. Renal graft function did not deteriorate more than in matched controls. A GH dose of 4 IU/m2/day proved adequate.

Adolescent↗
PubMed2001

Current concepts in tall stature and overgrowth syndromes.

In this overview an update is given on the pathogenesis, classification and differential diagnosis of overgrowth syndromes. In addition, height prognosis and therapeutic modalities available for managing mainly constitutional tall stature are discussed. Constitutional tall stature comprises normal variants in which one or both parents are tall. Primary disorders may have a prenatal onset and may be of chromosomal or genetic origin. Secondary overgrowth syndromes are most often the result of hormonal disturbances. Height prediction plays a key role in the management of tall children. Prediction equation models have been developed based on the growth data of healthy tall children. There is general agreement that a favourable effect on reducing ultimate height is obtained using high doses of sex steroids (girls 100-300 microg ethinyloestradiol; boys testosterone (T) ester depot preparations 250-1000 mg/month), the height reduction being greater when the treatment is started at a lower chronological and/or bone age. An alternative is the induction of puberty with low doses of sex steroids (girls 5-50 microg ethinyloestradiol; boys T esters 25-50 mg/m2/3 wk). In addition orthopaedic procedures have been suggested, but there is limited experience. Although psychosocial factors constitute the main reason for treating tall stature, extensive psychological investigations before or during height limiting therapy are lacking. Moreover, there are no objective data indicating lifelong psychosocial damage resulting from being tall.

Adolescent↗
PubMed2000

Detection of mutations in the ALD gene (ABCD1) in seven Italian families: description of four novel mutations.

The study describes the mutations causing adrenoleukodystrophy in seven Italian families. Four missense mutations leading to amino acid substitutions, two frameshift mutations leading to a premature termination signal, and a splicing mutation were identified. Mutations 2014C>T (P543L), 2053A>G (Q556A), 673-674insCC, and 1874+1G>A are described for the first time in this report. Mutations 1638C>T (R418W), 1588G>A(R401Q), and 1801-1802delAG are already known to be link to ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed2000

Susceptibility to oxidation of plasma low-density lipoprotein in X-linked adrenoleukodystrophy: effects of simvastatin treatment.

This paper shows for the first time the higher oxidizability of low-density lipoprotein (LDL) in plasma from adrenoleukodystrophy (ALD) patients compared to that of control subjects. LDL oxidation susceptibility was assessed by conjugate diene formation, hydroperoxide and lipoperoxide formation, and electrophoretic mobility. Simvastatin therapy, an HMG-CoA reductase inhibitor, seems to be a protective pharmacological agent against the higher oxidizability of LDL in plasma from ALD patients.

Adrenoleukodystrophy↗
PubMed2000

Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children.

The hormonal diagnosis of GH deficiency in childhood is conventionally based on the GH response to at least two provocative stimuli. Among these, arginine (ARG) has long been considered a classical, centrally mediated stimulus of GH secretion. ARG is also able to potentiate the GH response to GHRH, likely inhibiting hypothalamic somatostatin; this combined test is one of the most potent to explore the maximal secretory capacity of somatotroph cells. Based on these premises, we verified whether the sequential administration of ARG and ARG+GHRH could be feasible as single step provocative test to evaluate the GH releasable pool in short children. To this goal, 48 normal short children (35 M and 13 F, 12.0+/-0.4 yr, PS 1: 255 II-IV: 23) underwent a test with ARG (0.5 g/kg i.v. from 0 to +30 min) followed by a coadministration of ARG (from +120 to 150 min) plus GHRH (1 microg/kg i.v. at +120 min). ARG alone elicited a clear GH response (mean peak vs baseline: 12.1+/-1.7 vs 2.0+/-0.4 microg/l, p<0.001, Cmax range 12-51.0 microg/l). Following this GH rise, the hormonal levels at +120 min approached to baseline levels (4.2+/-0.8 microg/l) but then showed marked response to the coadministration of ARG+GHRH. The GH peak following ARG+GHRH (mean peak: 47.8+/-3.3 microg/l, p<0.001; Cmax 22.4-150.0 microg/l) was clearly higher (p<0.001) than that recorded after ARG alone. The GH responses to both ARG and ARG+GHRH were independent of gender, puberty, height velocity, body mass index (BMI) and IGF-I levels. Nine normal short children (16%) had GH peaks lower than 7 microg/l after ARG alone, while none showed GH peak below 20 microg/l after ARG+GHRH. Thus, ARG alone is a good stimulus of GH secretion but false positive responses frequently occur in normal short children. ARG+GHRH is a more potent stimulus giving no false positive responses even after previous challenge with ARG alone. Testing with sequential administration of ARG and ARG+GHRH may allow the single step evaluation of the somatotroph response to central and pituitary stimuli in short children.

Arginine↗
PubMed2000

Hyperparathyroidism during growth hormone treatment: a role for puberty?

We describe three adolescent patients on chronic hemodialysis with a pubertal growth spurt who developed severe hyperparathyroidism during recombinant human growth hormone treatment. Parathyroid hormone levels were raised in parallel with the increase in linear growth in all patients. In two patients, hyperparathyroidism was successfully controlled with an increase in calcitriol dosage. In the third patient, growth hormone had to be withdrawn. We discuss the possibility that puberty is a risk factor for the development of hyperparathyroidism during growth hormone therapy.

Adolescent↗
PubMed2000

Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome.

The Aarskog syndrome or facio-genital dysplasia (FGDY, MIM No. 305400) is an X-linked condition characterized by short stature, macrocephaly, facial, genital and skeletal anomalies. It is caused by mutation of the FGD1 gene mapped to the Xp11.21 region. To date, only one point mutation has been reported in an affected family, consisting of the insertion of an additional guanine residue at nucleotide 2122 of exon 7, which causes premature translational termination. We now report the finding of two novel FGD1 mutations, a missense mutation in a family of Italian origin and a deletion of 3 exons in a sporadic case from Germany. These mutations confirm the role of FGD1 as the gene responsible for the Aarskog syndrome.

Abnormalities, Multiple↗
PubMed2000

Neuroregulation of growth hormone during exercise in children.

Physical exercise is an important physiological stimulus to growth hormone (GH) release in man. Many neurotransmitters are involved in GH regulation. We studied the effect of the cholinergic pathway on GH secretion induced by physical exercise. Particularly, we studied the effect of a cholinergic muscarinic agonist on GH-induced physical exercise, both in children and adults. Moreover, we investigated the refractoriness of GH secretion after a second physical exercise stimulus. Three different protocols were performed: 1) GH response to physical exercise in children and adults; 2) effect of pyridostigmine on exercise-induced GH secretion in children and adults; 3) GH response to two consecutive exercises in children and adults. Our data show that in children GH peak after physical exercise is higher than in adults. Pyridostigmine enhances GH release in children and in adults. Exercise stimulus was able to release GH in the second test only in children, while the refractory phase did not permit a new GH release in adults. The shift to a modality of neural control of GH secretion peculiar of adults is likely due to neuroregulatory mechanisms which may be partly dependent on long-term variation in hormonal milieu.

Adolescent↗
PubMed2000

Novel point mutation in the splice donor site of exon-intron junction 6 of the androgen receptor gene in a patient with partial androgen insensitivity syndrome.

Androgen receptor (AR) gene mutations have been shown to cause androgen insensitivity syndrome with altered sexual differentiation in XY individuals, ranging from a partial insensitivity with male phenotype and azoospermia to a complete insensitivity with female phenotype and the absence of pubic and axillary sexual hair after puberty. In this study we present an 11-yr-old XY girl, with clinical manifestations peculiar for impaired androgen biological action, including female phenotype, blind-ending vagina, small degree of posterior labial fusion, and absence of uterus, fallopian tubes, and ovaries. At the time of the diagnosis the patient had a FSH/LH ratio according to the puberal stage, undetectable 17beta-estradiol, and high levels of testosterone (80.1 ng/mL). After bilateral gonadectomy, performed at the age of 11 yr, histological examination showed small embryonic seminiferous tubules containing prevalently Sertoli cells and occasional spermatogonia together with abundant fibrous tissue. Molecular study of the patient showed a guanine to thymine transversion in position +5 of the donor splice site in the junction between exon 6 and intron 6 of the AR gene. The result of RT-PCR amplification of the AR messenger ribonucleic acid from cultured genital skin fibroblasts of the patient suggests that splicing is defective, and intron 6 is retained in most of the receptor messenger ribonucleic acid molecules. We show by immunoblotting that most of the expressed protein lacks part of the C-terminal hormone-binding domain, and a small amount of normal receptor is observed. This is probably responsible for the reduced binding capacity in genital skin fibroblasts of the patient. The molecular basis of the alteration in this case is a novel, uncommon mutation, leading to a phenotype indicative of a partial androgen insensitivity syndrome, Quigley's grade 5.

Androgen-Insensitivity Syndrome↗
PubMed1999

Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy.

OBJECTIVE: To monitor the effects of dietary treatment in adult-onset adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). BACKGROUND: SEPs and MEPs have proved useful in revealing signs of progressively severe, central dying-back axonopathy in early stages of adult-onset ALD. METHODS: Eight patients with adult-onset ALD underwent clinical examination, brain and spine MRI, and SEP and MEP studies before and after 3 years of Lorenzo's oil dietary therapy. RESULTS: Before treatment, brain MRI was normal in five patients. Three of these patients had pure spinal SEP abnormalities and in the remaining two patients SEPs showed signs of involvement of both the spinal and cerebral somatosensory tracts. After treatment, the three patients with pure spinal abnormalities showed clinical and neurophysiologic worsening, whereas the two patients with a more advanced stage of disease (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic features. The patients with abnormal brain MRI at the onset of treatment showed clinical and neurophysiologic worsening. CONCLUSIONS: Lorenzo's oil therapy had no effect on patients with evidence of inflammatory brain lesions. Moreover, in patients without clear signs of inflammatory damage, this treatment does not modify significantly the natural course of the disease. However, because effective treatments should begin before the onset of severe neurologic symptoms, SEPs and MEPs should be considered to evaluate the effectiveness of other experimental treatments in the patient with a negative brain MRI.

Adrenoleukodystrophy↗
PubMed1999

Two novel missense mutations causing adrenoleukodystrophy in Italian patients.

The authors present two new missense mutations in exon 1 of the adrenoleukodystrophy (ALD) gene. The first, a C813T transition, results in the substitution Pro143 Ser in the third putative transmembrane domain of the adrenoleukodystrophy protein (ALDP) in an adult onset case. The second, a de novo C709T transition, results in a substitution Ser 108 Leu between the second and the third putative transmembrane segments, in a childhood case.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1999

Somatostatin infusion withdrawal: studies in normal children and in children with growth hormone deficiency.

Withdrawal of a somatostatin infusion (SSIW) is followed by a rebound rise of GH in both animals and normal adult men, a phenomenon likely mediated by endogenous GHRH function. In the present study, we have evaluated the GH response to SSIW in a group of 28 prepubertal children (18 boys and 10 girls; aged 3.7-11.1 yr). Six children had GH deficiency [GHD; GH responses to pyridostigmine (PD)+GHRH and to clonidine <20 and <7 microg/L, respectively], 4 children had GH neurosecretory dysfunction (GHND; GH responses to PD+GHRH and to clonidine > or =20 and >7 microg/L, respectively; mean integrated nighttime GH concentrations <3 microg/L), and 18 children were short normal children [normal controls (NC)]. All children received a constant infusion of SS at the dose of 3 microg/Kg x h for 90 min. SSIW elicited a clear-cut GH rise in NC children (13.7+/-1.0 microg/L), but not in GH-deficient children, regardless of the underlying etiology (GHD, 1.6+/-0.4 microg/L; GHND, 2.4+/-0.3 microg/L). The GH response to SSIW was similar between GHD and GHND children. There was no overlapping of the maximum SSIW-stimulated GH peaks between NC and GHD or GHND children. In conclusion, we have demonstrated that SSIW elicits a significant GH rise in NC children, but not in GH-deficient children, regardless of the underlying etiology (GHD or GHND). This resulted in complete discrimination of NC from GHD or GHND children. Were these present findings confirmed on a larger number of children, SSIW, because of its testing efficaciousness and safety, procedural simplicity, and economy holds promise of being a useful diagnostic tool for GH-dependent growth disorders.

Adrenergic alpha-Agonists↗
PubMed1998

Nonsyndromal overgrowth in males with mild psychomotor delay.

Over the last 3 years we ascertained 42 patients for statural overgrowth and/or macrocephaly, who also had mild developmental delay. There were 39 males and three females, two of whom were sisters. In no case was tall stature a familial characteristic. Family history was unremarkable, except for the case of the two sisters. Physical examination did not demonstrate any consistent pattern of malformations or anomalies identifying a syndrome, known or unknown. Chromosomes were apparently normal and the molecular test for the fragile X syndrome yielded normal results in all cases. Muscular hypotonia, advanced bone age, and epilepsy were relatively consistent manifestations. The hypothalamus-pituitary axis seemed to be intact when tested through the blood levels of insulin-like growth factors I and II and of the insulin-like growth binding protein 3, and the excess of growth was apparently growth hormone independent. The condition comprising excessive growth, developmental delay, muscular hypotonia, absence of a consistent pattern of physical anomalies, and apparently sporadic occurrence, largely limited to males, may be heterogenous.

Adolescent↗
PubMed1998

X-linked adrenoleukodystrophy: first report of the Italian Study Group.

In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.

Adolescent↗
PubMed1998

The growth hormone response to hexarelin in patients with Prader-Willi syndrome.

Hexarelin (Hex) is a synthetic hexapeptide with potent GH-releasing activity in both animals and men. Aim of this study was to evaluate the GH response to a maximal dose of Hex and GH-releasing hormone (GHRH) in a group of patients with Prader-Willi syndrome (PWS). Seven patients (4 boys and 3 girls, age 2.4-14.2 yr) with PWS, 10 prepubertal obese children (7 boys and 3 girls, age 7.5-12.0 yr), and 24 prepubertal short normal children (11 boys and 13 girls, age 5.9-13 yr) with body weight within +/- 10% of their ideal weight were studied. All subjects were tested on two occasions with GHRH 1-29 at the dose of 1 microgram/Kg i.v., and with Hex at the dose of 2 micrograms/Kg i.v. In the PWS patients the GH response to GHRH (peak = 6.4 +/- 2.0 micrograms/l, p < 0.0001; AUC = 248 +/- 70 micrograms min/l, p < 0.0001) was significantly lower than that observed in the short normal children and similar to that observed in the obese children. In the PWS children the GH response to Hex (peak = 7.5 +/- 1.6 micrograms/l; AUC = 309 +/- 53) was similar to that observed after GHRH and significantly lower than that observed in the obese children (p < 0.05). The results of this study show that PWS patients have a blunted GH response to the administration of a maximal dose of Hex. Whether these findings reflect a more severe pituitary GH deficiency in PWS than in obese children or a deranged hypothalamic regulation of GH secretion need further investigation.

Adolescent↗