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Biomedical subjects

C Angelini

Publications and source records attributed to C Angelini.

At least 55 records · Page 3Linked to original sources
PubMed2001

Epidemiology of myotonic dystrophy in Italy: re-apprisal after genetic diagnosis.

Before the discovery of the myotonic dystrophy (DM) gene, the DM epidemiological rates could not be accurately estimated. The aim of this study was to calculate the DM prevalence rates in Padova (North-East Italy) and in four provinces of North-West Tuscany (Central Italy) and, as of 30 June 1999, to do so using molecular genetic testing. A minimum prevalence rate of 9.31x10(-5) inhabitants was found, consistent with epidemiological rates worldwide, and more than two times as high as those of two previous studies conducted in the same areas during the era prior to molecular genetic testing. This study, the first in Italy since the discovery of the DM gene, underlines the importance of direct genetic diagnosis of DM, especially in detecting mildly affected patients, a fundamental step in correctly estimating the risk of disease transmission in affected families.

Adolescent↗
PubMed2001

Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and facioscapulo human muscular dystrophy. A potential target for pharmacological treatment?

Apoptosis was detected in different muscular diseases, including severe dystrophin deficiency, but apoptotic mechanisms are not completely described in adult skeletal muscle. Studying patients affected by Duchenne muscular dystrophy (DMD) and by facio-scapulo-humeral dystrophy (FSHD) we showed an increase of apoptotic myonuclei, bax, and bcl-2-positive myofibers. Positive correlation was detected between apoptotic nuclei and bax expression (p < 0.01). Expression of caspases was analyzed by RNase protection. Caspase transcript was not detected in normal skeletal muscles. DMD muscles expressed caspase 8, 3, 5, 2, 7 and Granzyme B mRNAs. Low levels of caspase 6, 3, and Granzyme B transcripts were detected in FSHD patients. Tissue levels of caspase 3 protein significantly correlated with apoptotic myonuclei (p < 0.05) and with bax expression (p < 0.01). In all DMD cases the activity of caspase 3 was increased, while the FSHD samples were heterogeneous. These data indicate that human skeletal muscle fibers. during the dystrophic process, modulate the expression of caspases and that caspase 3 is involved in myofiber cell death. opening new perspective in the pharmacological treatments of muscular dystrophies, such as the use of caspase inhibitors.

Adolescent↗
PubMed2001

Synthesis of the signal molecule acetylcholine during the developmental cycle of Paramecium primaurelia (Protista, Ciliophora) and its possible function in conjugation.

We recently discovered, in mating-competent Paramecium primaurelia, the presence of functionally related molecules of the cholinergic system: the neurotransmitter acetylcholine (ACh), both its nicotinic and muscarinic receptors and its lytic enzyme acetylcholinesterase (AChE). Our results on the inhibition of mating-cell pairing in vivo in mating-competent cells treated with cholinomimetic drugs support the hypothesis that the cholinergic system plays a role in cell-to-cell adhesion. To investigate the possible function of the signal molecule ACh in conjugation in P. primaurelia, we attempted to detect the intracellular sites of ACh synthesis by localizing the ACh biosynthetic enzyme choline acetyltransferase (ChAT). Using immunocytochemical and histochemical methods, we have demonstrated the presence and activity of ChAT principally on the surface membrane of mating-competent cells and of mature but non-mating-competent cells. No evidence for ChAT activity was found in immature cells. Immunoblot analysis revealed the presence of immunoreactive bands, ranging in molecular mass from 42 to 133 kDa, as reported for ChAT isolated from higher organisms. In vivo experiments showed that inhibition of ChAT activity by Congo Red, known to be a potent competitive inhibitor of acetyl coenzyme A, did not affect mating-cell pairing. Conversely, inhibition of AChE with BW 284c51 or eserine, which block enzyme activity by reacting with a specific serine within the catalytic centre, significantly inhibited mating-cell pairing. Our results suggest that ACh has a negative modulating effect on conjugation in P. primaurelia.

Acetylcholine↗
PubMed2001

[Stomach lymphoma].

BACKGROUND: Primitive gastric lymphoma (PGL) is a rare tumour, and although its incidence is rising it is difficult to state the role of the various therapeutic methods in treating this disease. Aim of this study is to point out what sequence of treatment is more effective trying to find out some guidelines which can be useful in clinical practice. METHODS: Retrospective analysis of clinical data of 54 patients with PGL admitted at a University surgical department during 10 years. All the patients underwent neoadjuvant or adjuvant chemotherapy and D2 gastrectomy. Follow-up ranged from 6 to 120 months. Survival was related to: Mushoff's stage of disease, the grade according to the Working Formulation and the sequence of treatment. Statistical analysis was performed by Kaplan-Maier method and the difference between survival curves was compared by log-rank test. RESULTS: Mean postoperative hospital stay was 12 days and morbidity was 18%. Five and 10 years overall survival rates were 70 and 85%. There was a significant difference in survival between patients with high grade PGL and those with intermediate grade (p=0.0188) as well as in those with low grade (p=0.0435). Patients in stages IE-II1E had a significantly longer survival than those in stages IIIE-IVE (p=0.0123). Patients in stages IE-II1E underwent neadjuvant chemotherapy and surgery and survived longer than those in whom surgery preceded chemotherapy (p=0.0293) instead for patients in stages IIIE-IVE neoadjuvant chemotherapy shortened survival (p=0.0403). CONCLUSIONS: In personal opinion, in patients in stages IE-II1E chemotherapy should be carried out before surgery, while in those in stages IIIE-IVE the reverse scheme is more effective in achieving longer survival rates.

Adult↗
PubMed2001

[Serious complications of vertical banded gastroplasty. Case report].

Vertical banded gastroplasty, reported by Mason in 1982, is an effective method to control pathologic obesity (BMI>40 kg/m2). With the widespread of this procedure and the introduction of laparoscopic approach several complications are described in literature: gastroesophageal reflux, esophagitis, gastritis, gastric bleeding and perforations, prolonged vomit, dislocation of gastric ring, cholelithiasis, gastric fistulas, gastric stomal stenosis, dehiscence of vertical stomach staple line. From 2 to 10% of patients are reoperated because of inefficacy of treatment or short and long-term complications. Morbidity and mortality associated to reoperations are still high and it is difficult to identify criteria for an appropriate revision procedure. This can occur through endoscopy, laparotomy or laparoscopy, depending on clinical and radiologic feature. Dehiscence of vertical stomach staple line, observed in 10-20% of cases, even if asymptomatic, can lead to bad complications such as fistulas, peritonitis and sepsis. The case of a young woman, who underwent a vertical banded gastroplasty for pathologic obesity (117 kg, h 167 cm, BMI 42/m2) and subsequent laparotomies in the attempt to correct vertical staple line dehiscence, is reported. The patient came to our observation in a septic shock caused by peritonitis and ARDS and a total gastrectomy with Roux-en-Y esophago-jejunostomy was performed.

Adult↗
PubMed2000

A novel laminin alpha2 isoform in severe laminin alpha2 deficient congenital muscular dystrophy.

OBJECTIVES: Laminin alpha2 deficiency presents at birth with muscle weakness, hypotonia, and usually asymptomatic white matter signal on MRI. Few patients with laminin alpha2 deficiency have been described with seizures and structural brain abnormalities. The reason for the variation in the severity of the clinical phenotype in congenital muscular dystrophy (CMD) with laminin alpha2 deficiency is not known. METHODS: A patient with CMD with partial laminin alpha2 presenting with brain structural abnormalities and untreatable generalized and partial complex seizure was studied. Alternative laminin alpha2 splicing was studied by single-strand conformational polymorphism/sequencing analysis. RESULTS: A novel laminin alpha2 isoform was identified. Nonsense laminin alpha2 mutations (stop codons) were inherited from both parents; however, one of the nonsense mutations was in a region of exon 31, which is alternatively spliced. The alternatively spliced isoform excluded one of the stop codon mutations, and was thus able to produce normal laminin alpha2 corresponding to this isoform. Laminin alpha2 immunofluorescence showed that this isoform was not evenly distributed at the muscle fiber basal lamina, but preferentially localized in discrete areas. Laminin alpha5, beta1, gamma1, and nidogen showed decreased expression by immunofluorescence. CONCLUSIONS: The severity of this patient's phenotype may be due to overexpression of the exon 31-spliced laminin alpha2 isoform. Exon 31 lies in the IIIA domain of the laminin alpha2 protein, just proximal to the triple coil-coiled region. It is possible that chain assembly is impaired by this isoform, resulting in a loss of possible rescue mechanisms.

Adolescent↗
PubMed2000

A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy.

We randomized 18 Duchenne muscular dystrophy (DMD) boys whose age ranged from 5.2 to 14.6 years (mean, 7.3 years) for treatment with either deflazacort (0.9 mg/kg/day) or prednisone (0.75 mg/kg/day) on the basis of age and functional score at the onset of treatment. We followed the patients every 3 months for 1 year, evaluating four limb muscles with the Medical Research Council scale and performance of four functions (walking, climbing stairs, Gowers' maneuver, and rising from a chair). Side effects were monitored by a questionnaire and by routine blood examination, and weight and height were recorded at each visit. At 12 months, the effect of both steroids was examined by comparing the status of the treated patients with another group of untreated DMD patients that served as natural history control. The two steroids were equally effective in improving motor function and functional performances. At 9 months, the average weight increase with respect to baseline value was 5% (2 kg) in the deflazacort group but 18% in the prednisone group (P < 0. 005), and the change remained significant after 12 months (P < 0.05). Other minor but nonsignificant side effects were observed. Steroid treatment with deflazacort appears to cause fewer side effects than with prednisone, particularly weight gain, which could be important to maximize motor performances.

Adolescent↗
PubMed2000

Private beta- and gamma-sarcoglycan gene mutations: evidence of a founder effect in Northern Italy.

Autosomal recessive muscular dystrophies called "sarcoglycanopathies" result from mutations in the genes encoding alpha-, beta-, gamma-, or delta-sarcoglycan complex components. The present study involved six unrelated families from Northern Italy showing mutations in the beta- or gamma-sarcoglycan genes. An 8 bp duplication in the beta-sarcoglycan gene and 1 bp insertion in the gamma-sarcoglycan gene occur with high frequency in our population. These mutations have never been reported thus far in other countries. Many patients are homozygotes for a single mutation, although they derived from non-consanguineous marriages. We suggest that these alleles are "private" mutations of this geographical region. A panel of highly informative microsatellite markers that map in the beta- and gamma-sarcoglycan gene locus was used to assess the haplotypes among affected patients and control population, in order to test the presence of linkage disequilibrium. We found that the 8 bp duplication in the beta-sarcoglycan gene and the 1 bp insertion in the gamma-sarcoglycan gene are in linkage disequilibrium with neighbouring polymorphisms. The recurrence of specific sarcoglycan mutations in Northern Italy is probably due to a founder effect, combined with a relative genetic isolation.

Alleles↗
PubMed2000

Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents.

PURPOSE: To evaluate the incidence and entity of muscle damage after hyperthermic limb perfusion (HLP) with doxorubicin or melphalan, two widely used chemotherapeutic agents. METHODS: We collected muscle biopsies from eleven patients with lower limb sarcoma or melanoma immediately before and at a variable time after the chemotherapeutic procedure (mean = 49.4 days). Biopsy specimens were stained with standard histochemical and immunohistochemical methods on cryostat sections and the grade of fiber atrophy was calculated. RESULTS: Clear neurogenic alterations were present in pre-HLP biopsies of seven patients related to age and previous therapy. In six patients, the comparison between biopsies before and after HLP demonstrated worsening of preexisting neurogenic condition and appearance of mitochondrial-related damage. Reduction in type I or type II fiber diameter was present in nine patients, but no relation to doxorubicin or melphalan treatment was clear. An unexpected, large accumulation of desmin was detected in the muscle biopsy of one patient receiving doxorubicin, probably related to the mechanism of doxorubicin-induced myotoxicity. CONCLUSIONS: The observed neuromuscular toxic effects could be related to the physical or chemical conditions of HLP, in particular perfusion temperature; in addition, the present study demonstrates that preexisting neuromuscular changes, i.e. neuropathy, modulates the degree of further damage following HLP.

Adult↗
PubMed2000

New therapies in muscular dystrophies.

Muscular dystrophies are a group of hereditary muscle disorders that often result in severe disability. Curative therapy is not yet available for muscular dystrophies (MD). In the near future, it is not expected that gene-replacement therapy will be available. Other strategies to decrease the rate of muscle necrosis and to increase strength in patients are necessary. Therefore the interest in symptomatic drug treatment has recently increased. A few trials have been performed on different types of muscular dystrophies, and some have generated positive results on muscle strength or muscle mass. We review the state of the art in therapy of MD and summarize the drugs that have been used and the evidence and results of such clinical trials.

Clinical Trials as Topic↗
PubMed2000

Correlation of clinical function and muscle CT scan images in limb-girdle muscular dystrophy.

Knowledge of selective muscle-involvement is useful to the clinician. Therefore we investigated in sarcoglycanopathy and dysferlinopathy: (i) the correlation between clinical scale, MRC scale and CT findings and (ii) the muscles involved. Patients with a definite diagnosis of dysferlinopathy and sarcoglycanopathy were tested for their clinical functions and muscle strength and assigned a functional grade. Nineteen muscles were evaluated by CT. In dysferlinopathy, distal lower-limb muscles are involved, while in sarcoglycanopathy proximal muscles are more affected. In both groups, muscles with MRC < 3 often had severe abnormalities on CT imaging, while muscles with MRC > 4 could be either normal or abnormal. Dysferlinopathy and sarcoglycanopathy have different and selective muscle involvement. This may affect certain types of functional activity. There is a possible relationship between CT findings and MRC grade in muscles with a low (< 3) MRC grade. Abnormality on CT scan may precede the clinical symptoms.

Adult↗
PubMed2000

Hereditary spastic paraplegia associated with peripheral neuropathy: a distinct clinical and genetic entity.

Hereditary motor and sensory neuropathy type V is a very rare disease in which hereditary spastic paraplegia is associated with peripheral motor and sensory neuropathy. The symptomatic onset of the disorder is usually in the second decade of life or later and the course is progressive over many years. Hereditary motor and sensory neuropathy type V is inherited as an autosomal dominant trait usually showing incomplete penetrance. So far, no molecular data are available in the literature about this disease. In our study we present clinical and molecular data from a large Italian family displaying hereditary motor and sensory neuropathy type V. Taking into account the clinical features in this family, we have performed a linkage analysis for markers strictly associated with all the known loci for autosomal dominant and autosomal recessive forms of hereditary spastic paraplegia and hereditary motor and sensory neuropathy type II, and have found no linkage to these loci. Our study suggests that hereditary motor and sensory neuropathy type V is not only a distinct clinical entity but also a distinct genetic entity.

Adult↗
PubMed2000

Acute quadriplegic myopathy in a 17-month-old boy.

Acute quadriplegic myopathy is a rare condition associated with the use of nondepolarizing muscle-blocking agents and corticosteroids in the course of severe systemic illness. A 17-month-old boy underwent liver transplantation for fulminant hepatitis. He was intubated for 24 days and treated with vecuronium bromide and high-dose methylprednisolone. The child was weaned from the ventilator and presented extreme weakness in the upper limbs and total paralysis of the lower limbs. Serum creatine kinase level was normal and electromyography showed myopathic abnormalities. Muscle biopsy showed severe type-1 fiber atrophy and selective loss of myosin thick filaments was seen on electron microscopy. Scattered regenerating fetal myosin-positive fibers were present, mu calpain was absent, while m calpain was diffusely expressed. Physical therapy was immediately started and the child recovered even though corticosteroids were not discontinued. The pathogenesis of acute quadriplegic myopathy is still unknown. We suggest that it could be due to abnormal protein turnover in the muscle. Several independent factors, such as corticosteroid treatment, immobilization, or cytokines, could take part in a cascade of events that leads to an excessive yet selective degradation of proteins involving myosin thick filaments and possibly components of sarcolemma, causing muscle inexcitability.

Anti-Inflammatory Agents↗
PubMed1999

Cognitive impairment and (CTG)n expansion in myotonic dystrophy patients.

BACKGROUND: Myotonic dystrophy (DM) is a genetic multisystemic disease with muscular, endocrine, ocular, cardiac and cognitive impairment. The molecular basis of the disease has been identified in an unstable base triplet (CTG)n repeat located in the 3' untranslated region of the miotonin protein-kinase (MT-PK) gene on the long arm of chromosome 19. Cognitive impairment could be a direct expression of this genetic alteration at the central nervous system (CNS) level rather than a consequence of the neuromuscular impairment. To explore this hypothesis, we tested a group of genetically diagnosed, adult onset DM, of their nonaffected relatives (NAR), of patients with spinal muscle atrophy (SMA), and of normal controls using the Wechsler Adult Intelligence Scale (WAIS). METHODS: Seventeen adult-onset DM patients, 9 NAR, 10 SMA patients and 20 unrelated normal controls (NC) were studied. Clinical, neuromuscular and neuropsychiatric evaluation, which included WAIS and the Schedule for Affective Disorders and Schizophrenia (SADS), were performed on the four groups. DM, NAR and NC were also assessed by a neurophysiological (P300) evaluation. A DNA analysis was performed in DM and in NAR to measure presence and magnitude of CTG expansion. RESULTS: We found a statistically significant difference between verbal (p < .0003), nonverbal (p < .0001) and total (p < .0001) IQ of DM patients compared to IQs of NAR, SMA and NC. Seven out of 11 WAIS subtests were significantly and consistently lower in DM patients compared to SMA and/or NC. In DM patients there was a statistically significant negative correlation between nonverbal (r = -.68; p < .002) and total (r = .59; p < .01) IQ and (CTG)n. Patients with DM had a significantly lower P300 amplitude compared to NAR and NC. CONCLUSIONS: Our study indicates that in DM there is a mild but significant cognitive impairment which correlates with the degree of CTG expansion and it is not dependent on the neuromuscular impairment; however further studies with larger groups of patients and controls are suggested to confirm our results, due to the small sample size and to a possible effect of educational level in our patients.

Adolescent↗
PubMed1999

Regeneration in sarcoglycanopathies: expression studies of sarcoglycans and other muscle proteins.

We have studied the immunohistochemical expression of 14 different muscle proteins of the basal lamina, sarcolemma and cytoskeleton in primary sarcoglycanopathies (13 cases) and compared it with Duchenne dystrophy (6 cases) and myositis (5 cases). Sarcolemmal proteins (i.e. 4 sarcoglycans, beta-dystroglycan, dystrophin, beta-spectrin) were reduced both in sarcoglycanopathies and Duchenne dystrophy, because of structural and functional impairment of the plasma membrane. Sarcolemmal proteins are poorly expressed in regenerating fibers of all muscle disorders, due to a developmental delay or to an abnormal assembly. Laminins (alpha2 and beta chains) were preserved in all cases while utrophin was expressed in Duchenne muscle but not in sarcoglycanopathies. Regenerating fibers were studied with different markers (i.e. fetal myosin, desmin, vimentin, laminin alpha1). Fetal myosin positive fibers (as well as desmin and laminin alpha1), were significantly higher in Duchenne dystrophy (25%) than in age-matched sarcoglycanopathies (7%). Vimentin, a marker of early regeneration, was expressed at higher level in sarcoglycanopathies than in Duchenne dystrophy, suggesting in the former a lower extent of regeneration or a shorter regeneration cycle.

Adolescent↗
PubMed1999

Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.

OBJECTIVE: To determine the frequency of calpain III mutations in a heterogeneous limb-girdle muscular dystrophy (LGMD) population. BACKGROUND: Mutations of the calpain III gene have been shown to cause a subset of autosomal recessive LGMDs. Patient populations studied to date have been primarily of French and Spanish origin, in which calpain III may cause 30% of autosomal recessive MDs. The incidence of calpain III mutations in non-French/Spanish MD patients has not been studied thoroughly. No sensitive and specific biopsy screening methods for detecting patients with abnormal calpain III protein are available. Thus, detection of patients relies on direct detection of gene mutations. METHODS: The authors studied the calpain III gene in 107 MD patient muscle biopsies exhibiting normal dystrophin. Muscle biopsy RNA was produced for each patient, and the entire calpain III complementary DNA was screened for mutations by reverse-transcriptase PCR/single-strand conformation polymorphism using three different conditions. RESULTS: The authors identified nine patients (eight unrelated) with causative mutations. Six of the seven distinct mutations identified are novel mutations and have not been described previously. CONCLUSION: The results suggest that approximately 9.2% of patients in the heterogeneous population with an LGMD diagnosis will show mutations of the calpain III gene. Interestingly, two patients were heterozygous for a single mutation at the DNA level, whereas only the mutant allele was observed at the RNA level. This suggests that there are undetectable, nondeletion mutations that ablate expression of the calpain III gene.

Adolescent↗