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Biomedical subjects

A D'Amico

Publications and source records attributed to A D'Amico.

At least 19 recordsLinked to original sources
PubMed2006

Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy.

OBJECTIVE: To assess the efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy in a randomized, double-blind, placebo-controlled trial involving 10 Italian centers. METHODS: One hundred seven children were assigned to receive PB (500 mg/kg/day) or matching placebo on an intermittent regimen (7 days on/7 days off) for 13 weeks. The Hammersmith functional motor scale (primary outcome measure), myometry, and forced vital capacity were assessed at baseline and at weeks 5 and 13. RESULTS: Between January and September 2004, 107 patients aged 30 to 154 months were enrolled. PB was well tolerated, with only one child withdrawing because of adverse events. Mean improvement in functional score was 0.60 in the PB arm and 0.73 in placebo arm (p = 0.70). Changes in the secondary endpoints were also similar in the two study arms. CONCLUSIONS: Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.

Child↗
PubMed2006

Expanding the clinical spectrum of POMT1 phenotype.

Mutations in POMT1 have been identified in Walker-Warburg syndrome and in patients with limb-girdle muscular dystrophy and mental retardation (LGMD2K). The authors report new POMT1 mutations in three unrelated children with severe motor impairment, leg hypertrophy, and mental retardation but without brain and ocular malformations. These patients are similar to LGMD2K but have earlier onset and more severe motor disability. The current findings expand the spectrum of POMT1-associated phenotypes.

Adolescent↗
PubMed2006

POMT2 mutation in a patient with 'MEB-like' phenotype.

Mutations in POMT2 have so far only been reported in patients with Walker-Warburg phenotype. We report heterozygous POMT2 mutations in an a girl with a milder phenotype characterized by mental retardation, microcephaly, hypertrophy of the quadriceps and calf muscles, and structural brain changes mostly affecting the posterior fossa. Our findings suggest that, as previously reported for POMT1 and FKRP, mutations in the POMT2 can also be associated with clinical heterogeneity.

Amino Acid Sequence↗
PubMed2006

Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

The aim of this study was to validate the Hammersmith functional motor scale for children with spinal muscular atrophy in a large cohort of 90 non-ambulant children with spinal muscular atrophy type 2 or 3. All had a baseline assessment (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was > 95%. Of the 66 children examined after 3 months 4 had adverse effects in between assessments and were excluded from the analysis. Forty-two (68%) of the remaining 62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no variation in scores between T0 and T2 and another 9 (37.5%) had variations within +/- 1 point. Our study confirms previous observations of the reliability of the scale and helps to establish a baseline for assessing changes of functional ability over 3 and 6 month intervals. This information can be valuable in view of therapeutic trials.

Child↗
PubMed2005

Major myofibrillar changes in early onset myopathy due to de novo heterozygous missense mutation in lamin A/C gene.

Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular diseases and more complex syndromes, involving bone and adipose tissue. We report on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9, characterized by the presence of a marked number of cytoplasmic bodies with extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle. This case suggests there is a need to increase the list of genes to be screened in patients with myofibrillar myopathy.

Child↗
PubMed2005

The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.

Adolescent↗
PubMed2005

Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1 genes.

Dropped head syndrome is characterized by severe weakness of neck extensor muscles with sparing of the flexors. It is a prominent sign in several neuromuscular conditions, but it may also be an isolated feature with uncertain aetiology. We report two children in whom prominent weakness of neck extensor muscles is associated with mutations in lamin A/C (LMNA) and selenoprotein N1 (SEPN1) genes, respectively. This report expands the underlying causes of the dropped head syndrome which may be the presenting feature of a congenital muscular dystrophy.

Arginine↗
PubMed2005

Phenotypic heterogeneity in two unrelated Danon patients associated with the same LAMP-2 gene mutation.

Danon disease, an X-linked cardioskeletal myopathy caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2), is clinically characterized by cardiomyopathy, myopathy, and variable mental retardation. The pathological hallmark of the disease is the absence of LAMP-2 immunohistochemical staining in muscle. The LAMP-2 gene mutations reported thus far are generally private mutations. We describe two cases of Danon disease with different clinical presentation, in whom we identified the same exon skipping mutation c.928G>A in the LAMP-2 gene. The first patient was affected by an early onset myopathy and hypertrophic cardiomyopathy (HCM) that partially improved with drug treatment. A first muscle biopsy at age 4 months showed markedly increased glycogen, and acid maltase deficiency was ruled out biochemically. A second muscle biopsy, performed at age 3(1/2) years, showed very mild abnormalities. The second child at age 15 years had mild, diffuse muscle weakness and wasting, moderate mental deficiency, and HCM. Two serial biopsies performed at age 8 and 15 years showed similar findings of multiple esterase-positive vacuoles in type I myofibers. In both patients the immunohistochemical study demonstrated the absence of LAMP-2 in skeletal muscle.

Adolescent↗
PubMed2004

Piezoelectric sensors for dioxins: a biomimetic approach.

The aim of this work was to design a fast, cheap and easy to use analytical system for dioxins. Piezoelectric sensors coupled with the pentapeptides as biomimetic traps (the receptors), selective for the dioxins, were used for the realisation of this analytical system. A methodology to select specific receptors among all possible pentapeptides randomly generated was represented by the use of molecular modelling software. Three peptides called later on A, B and C (A:[N]Asn-Phe-Gln-Gly-Ile[C]; B:[N]Asn-Phe-Gln-Gly-Gln[C]; C:[N]Asn-Phe-Gln-Gly-Phe[C]), were selected and evaluated for their potential usage as artificial receptors in solid-gas analysis by using a quartz crystal microbalance (QCM) sensors array. The peptide sequences were functionalised by two terminal cysteine residues in order to achieve a covalent interaction with the QCM gold surface. A manganese-porphyrin complex and two other pentapeptides, a pentaglutamine (pentapeptide D) and a pentalysine (pentapeptide E), were used as negative control sensors. The QCM sensors (A, B and C) gave a good linearity against different sample concentrations of the 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) and a mixture of dioxins. In particular, the selectivity against 2,3,7,8-TCDD was nicely correlated to the estimated binding energy of the receptors calculated by computational modelling. The cross-reactivity of the system was quantified using commercial polychlorinated biphenyls (PCBs) mixtures (dioxin-like compounds).

Biomimetics↗
PubMed2004

Monitoring of biological odour filtration in closed environments with olfactometry and an electronic nose.

Air treatment with a compact biological membrane filter, and air quality monitoring with an electronic nose were tested in the laboratory on air from a cage containing six mice. Additional analyses of air to and from the filter were performed using olfactometry and ammonia and hydrogen sulphide gas detection tubes. The biological air filter is a module containing biofilm-coated membrane fibres that separate a closed liquid loop from a gas phase. Odour compounds and oxygen diffuse through the membranes from the gas phase to the biofilm, where they are degraded to carbon dioxide and water. The prototype "ENQBE" electronic nose is based on an array of eight thickness shear mode resonators (TSMR), also known in the literature as quartz microbalance sensors. The chemical sensitivity is given by molecular films of metalloporphyrins and similar compounds. Chemical interaction of compounds in the air with the vibrating sensors induces a frequency change of the vibration that can be measured as a signal. The air from the mouse cage had a strong odour (3490 OUE/m3). The biological membrane filter performed well, achieving over 80% odour and ammonia reduction. The electronic nose signal could be correlated with the inlet and outlet air-quality of the biological filter, making it a promising method for monitoring air quality in closed environments.

Air Pollutants↗
PubMed2003

The evolving role of androgen deprivation therapy in the management of prostate cancer.

Androgen deprivation therapy (ADT) plays a central role in the management of prostate cancer. ADT is the mainstay of treatment for metastatic disease; the most common method is gonadal suppression via luteinizing hormone release hormone (LH) agonists, with or without antiandrogens. Antiandrogen monotherapy remains investigational, as is the appropriate role of 5alphareductase inhibition for prostate cancer. Intermittent ADT offers the promise of improved quality of life and reduced cost without a decrease found to date in oncologic efficacy. A growing menu of options exists for secondary androgen deprivation after disease progression on primary therapy: these include high-dose antiandrogens, estrogens, and adrenal androgen suppressants. ADT is being used with increasing frequency as primary monotherapy in patients with localized disease, but only small, nonrandomized studies of highly selected patients have been reported to date. Neoadjuvant ADT (NADT) has been demonstrated in prospective, multi-institutional trials to improve outcomes for patients with high-risk or locally advanced disease undergoing external-beam radiotherapy. Trials for patients with lower-risk, localized disease are still ongoing. Neoadjuvant therapy does not improve outcomes for patients with localized disease opting for radical prostatectomy (RP) and has not been well studied in association with brachytherapy. The side effects of ADT can be managed increasingly successfully; in particular, the introduction of zoledronate may reduce the impact of ADT-associated osteoporosis. Finally, contemporary practice pattern data suggest that use of ADT is increasing across patient risk groups, both in contexts where such therapy is well supported by current evidence and in others where it is not.

Algorithms↗
PubMed2001

Development of thymic and splenic dendritic cell populations from different hemopoietic precursors.

The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8alpha, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin(-)c-kit(+)Thy-1(low)CD4(low)) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4(-)CD8alpha(+) DCs, whereas CMPs produced similar numbers of CD4(-)CD8alpha(+) and CD4(+)CD8alpha(-) DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8alpha does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

Animals↗
PubMed2001

Radiation and hormonal therapy for locally advanced and clinically localized prostate cancer.

Increasingly, radiation therapists are using neoadjuvant and/or adjuvant androgen deprivation therapy (ADT) in higher-risk patients who are receiving radiation therapy with curative intent. Studies supporting this combination therapy have shown a benefit in patients with locally advanced disease based on the relatively short follow-up time to report, to date. The differing study designs, patient selection criteria, and regimens used in these studies are reviewed and compared, along with the reported outcomes. Trials currently underway will examine the efficacy of ADT (4 to 6 months in duration) in patients with clinically localized prostate cancer with >/=1 high-risk features.

Androgen Antagonists↗
PubMed2001

Urinary N-acetyl-beta-D-glucosaminidase concentration in patients with spinal cord injury: relationship with urodynamic parameters.

OBJECTIVES: To investigate the relationships between urinary N-acetyl-beta-D-glucosaminidase (NAG) concentrations and urodynamic parameters in patients with spinal cord injury (SCI). NAG has been proposed as a marker of renal damage. METHODS: Twenty-three patients with SCI were evaluated with urodynamic studies. Urine samples were collected from the 23 patients and 10 healthy volunteers, the NAG levels were evaluated, and the urodynamic parameters were compared with the urinary NAG levels. The patients were divided into two groups according to the amplitude of the hyperreflexic detrusor contractions (HDCs): group A, patients with an HDC amplitude of 40 cm H(2)O or greater, and group B, patients with an HDC amplitude of less than 40 cm H(2)O; group C was composed of healthy volunteers. The urinary NAG concentrations in the three groups were compared. RESULTS: A positive correlation was found between the urinary NAG levels and the HDC amplitude and detrusor leak point pressure (P = 0.015 and 0.007, respectively). The urinary NAG concentration was 3.38 U/g in group A, 2.14 U/g in group B, and 2.12 U/g in group C. The differences in the urinary NAG concentrations between groups A and B and between groups A and C were statistically significant (P = 0.03 and P <0.001, respectively). The concentrations between groups B and C were comparable. CONCLUSIONS: In our experience, the only urodynamic parameters that clearly and positively correlated with the urinary NAG levels were those expressing the amplitude of intravesical pressure. This result stresses the importance of reducing the intravesical pressure in patients with SCI using alternative treatments or surgical procedures if the usual conservative therapies are not effective.

Acetylglucosaminidase↗