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Biomedical subjects

C Bruno

Publications and source records attributed to C Bruno.

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

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↗
PubMed2006

High plasma creatine kinase: review of the literature and proposal for a diagnostic algorithm.

The condition of persistently high plasma CK levels is frequently encountered in asymptomatic patients with normal neurological examination. This condition may be the unique manifestation of several neuromuscular disorders, whose diagnosis is now possible using new diagnostic techniques. However, even if these patients are intensely investigated, specific diagnoses are not always forthcoming. Because of the lack of a widely accepted diagnostic protocol, hyperCKaemia in asymptomatic subjects is a potentially difficult clinical problem. In this paper we review the literature on conditions associated with variations in plasma CK levels and the literature on investigations carried out in asymptomatic persons with high CK to identify neuromuscular diseases. In the light of these data, and the deliberations of a working group of the Italian Association of Myology, we propose a diagnostic algorithm to guide the diagnostic work-up of persons presenting with persistently high levels of plasma CK. This algorithm has been discussed and approved by the Committee of the Italian Association of Myology.

Algorithms↗
PubMed2006

Lipoid proteinosis: case report and review of the literature.

Lipoid proteinosis is a rare autosomal recessive disorder, characterized histologically by infiltration of periodic acid Schiff-positive hyaline material into the skin, upper aerodigestive tract, and internal organs. Classical clinical features include skin scarring, beaded eyelid papules, and laryngeal infiltration leading to hoarseness. Moreover, the infiltrates in the tongue and its frenulum limit lingual movements and cause speech difficulties. Usually, the hoarse voice is present at birth or in early infancy, as the first manifestation. In more severe cases, diffuse infiltration of the pharynx and larynx might cause respiratory distress, at times requiring tracheostomy. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene on chromosome 1q21. The function of the protein extracellular matrix protein 1 gene is still unclear, although an important role in skin physiology and homeostasis has been hypothesized. In this report, the case is described of a 6-year-old girl with lipoid proteinosis. Histopathological examination of a laryngeal biopsy specimen showed massive deposits of eosinophilic, periodic acid Schiff-positive, and diastase resistant material in the lamina propria corroborating the clinical diagnosis of lipoid proteinosis. Molecular analyses in this patient also confirmed the clinical diagnosis. The proposita was a compound heterozygote for a new small rearrangement (543de1TG/ins15) in exon 6, and a nonsense mutation (Arg243Stop) in exon 7. Together with previously documented mutations in the extracellular matrix protein 1 gene, this study supports the hypothesis that exons 6 and 7 are the most common sites for extracellular matrix protein 1 gene mutations in lipoid proteinosis.

Child↗
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

Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV).

BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity. OBJECTIVE: To identify the molecular bases of different neuromuscular forms of GSD-IV and to establish possible genotype/phenotype correlations. METHODS: Eight patients with GBE deficiency had different neuromuscular presentations: three had fetal akinesia deformation sequence (FADS), three had congenital myopathy, one had juvenile myopathy, and one had combined myopathic and hepatic features. In all patients, the promoter and the entire coding region of the GBE gene at the RNA and genomic level were sequenced. RESULTS: Nine novel mutations were identified, including nonsense, missense, deletion, insertion, and splice-junction mutations. The three cases with FADS were homozygous, whereas all other cases were compound heterozygotes. CONCLUSIONS: This study expands the spectrum of mutations in the GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically and genetically heterogeneous.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2004

Clinical and molecular findings in patients with giant axonal neuropathy (GAN).

Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder of early onset, clinically characterized by a progressive involvement of both peripheral and CNS. The diagnosis is based on the presence of characteristic giant axons, filled with neurofilaments, on nerve biopsy. Recently, the defective protein, gigaxonin, has been identified and different pathogenic mutations in the gigaxonin gene have been reported as the underlying genetic defect. Gigaxonin, a member of the BTB/kelch superfamily proteins, seems to play a crucial role in the cross talk between the intermediate filaments and the membrane network. The authors report clinical and molecular findings in five Italian patients with GAN. This study shows the allelic heterogeneity of GAN and expands the spectrum of mutations in the GAN gene. The frequent occurrence of private mutations stresses the importance of a complete gene analysis.

Adolescent↗
PubMed2004

Severe neonatal onset of glycogenosis type IV: clinical and laboratory findings leading to diagnosis in two siblings.

Glycogenosis type IV is an autosomal recessive disease, exceptionally diagnosed at birth: only very few reports of the fatal perinatal neuromuscular form have been described. We report on two sibling male newborns who died at 10 and 4 weeks of age with clinical signs of a systemic storage disease. Prenatal history included polyhydramnios, reduced fetal movements and fetal hydrops, and Caesarean section was performed at 36 weeks of gestational age because of fetal distress. At birth, both babies showed severe hypotonia, hyporeflexia and no spontaneous breathing activity. They never showed active movements, sucking and swallowing and were respirator-dependent until death. A muscle biopsy revealed, in both patients, the presence of PAS-positive and partially diastase-resistant cytoplasmic inclusions containing granular and filamentous amylopectin-like material. This suggested that the stored material consisted of abnormal glycogen. At autopsy, ultrastructural examination of cardiac and skeletal muscle, liver, kidney and brain showed PAS-positive diastase-resistant eosinophilic cytoplasmic inclusions. Determination of branching enzyme activity, in cultured fibroblasts from the second patient, showed markedly reduced enzyme activity, confirming diagnosis of glycogenosis type IV. Our patients showed the full spectrum of both prenatal signs (hydrops, polyhydramnios) and postnatal signs (hypotonia, hyporeflexia, absence of active movements, cardiomegaly), which have been reported previously. They suffered from a very severe form of glycogenosis type IV with clinical and histological involvement of many tissues and organs. Diagnosis was accomplished on the second baby and required several biochemical and histological studies, in order to rule out both neuromuscular disorders and the most common storage diseases with neonatal onset. In our experience, the correct interpretation of the histological findings was essential in the search for the diagnosis.

Age of Onset↗
PubMed2003

Long-term survival in Stuve-Wiedemann syndrome: a neuro-myo-skeletal disorder with manifestations of dysautonomia.

Stuve-Wiedemann syndrome (SWS) is a multiple congenital anomalies syndrome mostly considered to have an early lethality. Only few patients have been reported with long survival; therefore, the clinical phenotype with age has not yet been clearly characterized. We report on two patients with SWS aged 12 and 3 years who have both the osteodysplastic symptoms of the entity as well as autonomic nervous system symptoms resembling familial dysautonomia: lack of corneal reflex and neuropathic keratitis, absence of fungiform papillae, ulcerations of the tongue, paradoxical sweating at low temperature, patellar hyporeflexia, and progressive scoliosis. The clinical and radiological similarities between patients with SWS and patients with Schwartz-Jampel syndrome have led to the suggestion that these two syndromes are a single entity. SWS and Schwartz-Jampel syndrome type II are now indeed considered to be identical, but the radiographic phenotype of SWS long survivors such as the presently reported patients justifies the distinction between SWS and the classical type of Schwartz-Jampel syndrome. An increased number of lipid droplets in muscle fibers and decreased muscle mitochondrial enzyme activities have been found in one patient, confirming a previously reported association between SWS and respiratory chain abnormalities.

Abnormalities, Multiple↗
PubMed2003

Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene.

The authors report on a family with dominantly inherited progressive external ophthalmoplegia and a diagnostic and statistical manual (fourth revised edition) diagnosis of bipolar psychiatric disorder in several members. Skeletal muscle biopsy from the proposita showed decreased cytochrome c oxidase staining, several ragged-red fibers, and multiple mtDNA deletions. The authors identified a missense mutation (leucine 98-->proline) in the adenine nucleotide translocator 1 gene. The presence of bipolar affective disorder expands the phenotype of adenine nucleotide translocator 1 allelic variants.

Adenine Nucleotide Translocator 1↗
PubMed2003

Microsurgical spermatico-epigastric venous anastomosis in the treatment of varicocele in children: assessment of long-term patency.

AIM: To demonstrate the long-term patency of microsurgical anastomoses between the internal spermatic vein and the inferior epigastric vein, constructed in the treatment of essential varicocele in paediatric patients to supplement ligation of the spermatic veins. MATERIALS AND METHODS: We submitted 66 patients to inguinopelvic colour-flow Doppler ultrasonography. The patients had been treated 18 - 36 months earlier for essential varicocele by microsurgical inguinal ligation of the testicular venous pedicle and anastomosis between the internal spermatic vein and the inferior epigastric vein. RESULTS: Preoperatively, the 66 patients operated on at ages ranging from 10 to 16 years (13 +/- 1.4) presented with Dubin and Amelar grade II (14 patients) or grade III (52 patients) left varicocele with ipsilateral testicular hypotrophy. The postoperative follow-up showed 2 cases of persistence of disease and 3 cases of persistence of "medium" spermatic vein reflux without clinical evidence of varicocele. Seven patients developed left hydrocele which resolved spontaneously in 5 cases, whereas in 2 cases it proved necessary to perform an eversion of the tunica vaginalis of the testis. The results obtained in patients treated for Coolsaet type I varicocele (64 patients) were as follows: long-term patency of the anastomosis was observed in 58/64 patients (90.6 %); in 4 patients (6.2 %) the left inferior epigastric vein presented a position in relation to the homologous artery that prevented adequate sampling and thus made it impossible to assess the patency of the anastomosis; in 2 patients (3.1 %) the anastomosis was closed. In the two patients who had submitted to anastomosis for Coolsaet type III varicocele, colour-flow Doppler failed to identify the shunt. CONCLUSIONS: The results of this study demonstrate that microsurgical anastomosis between the internal spermatic vein, and the inferior epigastric vein remains competent in the long term, thus confirming the validity of this technique for the treatment of essential varicocele in children.

Abdominal Muscles↗
PubMed2003

Psychiatric comorbidity in a population of outpatients affected by tinnitus.

The aim of this study was to outline the psychopathological characteristics of a population of outpatients affected by tinnitus and to consider its impact on their mental state and ability to function in major areas of their lives. Seventy-five consecutive tinnitus patients were enrolled on their first visit to the outpatients clinic of the Audiology Department of the 'Federico II' University of Naples, for audiological and psychiatric evaluation. A series of audiometric and vestibular tests was performed for tinnitus rating assessment, and further information was obtained from the patient via a semi-structural interview. For the psychopathological examination, patients underwent the Mini International Neuropsychiatric Interview (MINI), by means of which a multiaxial diagnosis (five axes) was expressed, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). For a better understanding of the personality aspects, the Minnesota Multiphasic Personality Inventory (MMPI) test was administered to a subgroup of 55 subjects whose cultural background permitted their full cooperation. The results of the study show that 58 subjects (77% of the total) met the criteria for psychiatric disorder diagnosis, according to the DSM-IV system: Axis I comprises anxiety, affective and somatoform disorders and psychoses; Axis II comprises personality disorders. Multiple diagnoses were expressed in some subjects. The findings of the examination via MMPI show a high percentage of depression, hysteria, and hypochondria. Although we are not seeking to establish a cause-effect relationship between the unpleasant experience of tinnitus and psychopathological disorders, our findings are consistent with those of other authors. Tinnitus can indeed have severe consequences for the subject's ability to function in many areas of their life. In this paper, the implications of such results for the diagnosis and therapy of tinnitus are discussed.

Adult↗
PubMed2002

SPG3A: An additional family carrying a new atlastin mutation.

The authors report on a novel frameshift mutation (c.1688insA) in the SPG3A gene resulting in premature translation termination of the gene product atlastin. These data add a new variant to the second disease gene in autosomal dominant hereditary spastic paraplegia (ADHSP) and lend definitive support to its causative role. By combining direct testing of SPAST and SPG3A, at least 50% of ADHSP families can now receive appropriate genetic diagnosis.

Adult↗
PubMed2002

What happens to eating disorder outpatients who withdrew from therapy?

OBJECTIVE: Dropouts are frequent among eating disorder (ED) patients, but less is known about their natural history. This paper assesses the outcome of outpatients who dropped out from a therapy programme and its possible causes. MATERIAL AND METHODS: From 1992 to 1994, we assessed 222 ED subjects. Psychiatrists expert in EDs evaluated these subjects by defining baseline parameters and diagnosis was made according to the 3rd revisioned edition of the Diagnostic and Statistical Manual of Mental Disorders. One hundred and twenty-eight subjects (57%) dropped out during the treatment. In 1997, we contacted them, reassessed the same baseline parameters and asked for a self-judgment about their social and clinical condition during the previous 2-5 years. Patients were classified as "improved" and "not improved" (stationary or worse) according to their social, physical and psychological condition. The relation between baseline condition and outcome was determined statistically. RESULTS: Seventy-one percent of subjects were "improved" and no deaths were recorded. A significant correlation was found between "duration of illness" and no treatment following a dropout. DISCUSSION: The high percentage of improvement among dropouts was unexpected. Shorter duration of illness and lack of specific therapy in the improved patients suggest the existence of a subset of ED patients with acute onset and a spontaneous tendency to improve. This point obviously requires further investigation.

Adaptation, Psychological↗
PubMed2002

The role of sensory input in motor neuron sprouting control.

Primary sensory neurons project to motor neurons directly or through interneurons and affect their activity. In our previous paper we showed that intramuscular sprouting can be affected by changing the sensory synaptic input to motor neurons. In this work, motor axon sprouting within a peripheral nerve (extramuscular sprouting) was induced by nerve injury at such a distance from muscle so as not to allow nerve-muscle trophic interactions. Two different procedures were carried out: (1) sciatic nerve crush and (2) sciatic nerve crush with homosegmental ipsilateral L3-L5 dorsal rhizotomy. The number of regenerating motor axons innervating extensor digitorum longus muscle was determined by in vivo muscle tension recordings and an index of their individual conduction rate was obtained by in vitro intracellular recordings of excitatory postsynaptic end-plate potentials in muscle fibers. The main findings were: (1) there are more regenerated axons distally from the lesion than parent axons proximally to the lesion (sprouting at the lesion); (2) sprouting at the lesion was negatively affected by homosegmental ipsilateral dorsal rhizotomy; (3) the number of motor axons innervating extensor digitorum longus muscle extrafusal fibers counted proximally to the lesion increased following nerve injury and regeneration but this did not occur when sensory input was lost. A transient innervation of extrafusal fibers by gamma motor neurons may explain the increase of motor axons counted proximally to the lesion.

Animals↗
PubMed2002

Familial isolated hyperCKaemia associated with a new mutation in the caveolin-3 (CAV-3) gene.

An 18 year old man and his mother both presented with persistent, isolated raised serum creatine kinase (hyperCKaemia) without muscle symptoms. Analysis of caveolin-3 protein expression in muscle biopsy of the propositus showed a reduction in the protein. Genetic analysis revealed a new heterozygous mutation in the caveolin-3 (CAV-3) gene: a C-->T transition at nucleotide position 83 in exon 1 leading to a substitution of a proline for a leucine at amino acid position 28 (P28L). This is the first pathogenic mutation in the CAV-3 gene associated with isolated familial hyperCKaemia. It expands the genetic heterogeneity in patients with caveolin-3 deficiency and confirms that caveolin-3 deficiency should be considered in the differential diagnosis of isolated hyperCKaemia.

Adult↗