PubMed Health⌕ Search

Biomedical subjects

A Toscano

Publications and source records attributed to A Toscano.

At least 19 recordsLinked to original sources
PubMed2006

Amyloid myopathy presenting with rhabdomyolysis: evidence of complement activation.

At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000-1200U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy.

Aged↗
PubMed2006

Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL.

Glycogenosis type III (Cori disease) is an autosomal recessive disorder caused by the deficiency of the glycogen debranching enzyme, encoded by the AGL gene, and existing in six isoforms alternately spliced in a tissue-specific way. Generally, disease onset occurs early on starting from the first year of life, with hepatomegaly, hypoglycemia, hyperlipidemia, increased CK levels, and, in some cases, short stature and slight mental retardation. Frequently, hepatomegaly tends to resolve spontaneously and inexplicably during childhood, when myopathy, often associated with cardiomyopathy, arises. This disease is known to lack almost invariably clear links between the genotype and clinical phenotype. We describe nine new mutations in Italian patients: four nonsense (p.Arg285X, p.Lys422X, p.Arg910X, p.Arg977X), three frameshift (c.442delA, c.753_756delGACA, c.3963delG), and two missense (p.Ala1120Pro, p.Arg524His). Particularly, the nonsense p.Arg285X is linked to an exonic splicing enhancer and it was found to produce two species of transcripts at the same time. Moreover, we discuss a subgroup of subjects carrying c.2681+1G>A, which has proven to be the most frequent mutation among our patients. The previously described c.664+3A>G was also detected in two patients, both homozygous. The present work is yet another confirmation that the individual genetic background plays a pivotal role in influencing the phenotypes, as occurs in other metabolic diseases.

Adult↗
PubMed2005

Clinical and muscle magnetic resonance imaging study of an Italian family with autosomal dominant inclusion body myopathy not linked to known genetic loci.

The objective was to report a clinical, pathological and muscle magnetic resonance (MR) study of an Italian family with an autosomal dominant inclusion body myopathy (AD-IBM). Eight subjects (age range 20-56 years; 5 females and 3 males) belonging to four generations were studied. Onset of disturbances (distal weakness at lower limbs) ranged from 20 to 28 years. CK levels were increased to five times. Only in an early stage oedema of involved muscles has been demonstrated by muscle MR. Quadriceps femoris was characteristically spared; in the last phases a mild involvement of the vasti became evident with persistent sparing of the rectus femori. Rimmed vacuoles and hyperphosphorylated tau filaments were evident at muscle biopsy. Linkage analysis excluded the association of the disease to chromosome loci 14q11, 17p13.1, 2p13, 19p13. The study suggests that quadriceps sparing is a characteristic feature also of AD-IBM. This finding could represent a muscle-image hallmark helpful in diagnosis of autosomal dominant muscular disorders.

Adult↗
PubMed2005

Juvenile limb-girdle myasthenia gravis.

Limb-girdle myasthenia is a rare disorder which includes familial and autoimmune forms. Myasthenia gravis is an uncommon disease in children and its diagnosis may be difficult. We report here five cases of autoimmune juvenile LGM starting before the age of 16 years with attention to clinical diagnostic difficulties, evolution, laboratory and instrumental data as well as response to treatment. Diagnosis of limb-girdle myasthenia requires a strong index of suspicion also in childhood. We suggest that this form be suspected in children with unclassifiable myopathy, mostly affecting deltoid muscles and lower extremities.

Adolescent↗
PubMed2005

Fatal exacerbation of peripheral neuropathy during lamivudine therapy: evidence for iatrogenic mitochondrial damage.

A 57-year-old man with mild neuropathy who was positive for hepatitis B and C viruses was treated with lamivudine 300 mg.day(-1). After 3 months he presented with dysphonia and progressive muscle weakness. Subsequently, he developed tetraparesis followed by acute respiratory failure requiring mechanical ventilation, which was complicated by sudden cardiac arrest. After lamivudine was stopped, the neuropathy improved and respiratory capacity improved. Unfortunately, the patient died suddenly in spite of haemodynamic, ventilatory and metabolic support. Electrophysiological studies showed evidence of a sensory-motor axonal neuropathy. Nerve biopsy, muscle biopsy, biochemistry and mitochondrial DNA molecular genetics suggested possible widespread iatrogenic mitochondrial damage. Mitochondrial DNA dysfunction could be a potential cause of the sudden cardiac arrest. Stopping lamivudine treatment sooner after the onset of peripheral neuropathy or its exacerbation is important as continued therapy could lead to acute respiratory failure requiring mechanical ventilation and intensive care unit admission.

Fatal Outcome↗
PubMed2005

Specific matrix metalloproteinase expression in focal myositis: an immunopathological study.

OBJECTIVES: The aim of our study was to investigate immunoexpression of matrix metalloproteinases MMP2, MMP7 and MMP9 in muscle specimens from patients with focal myositis (FM) vs polymyositis (PM) and dermatomyositis. MATERIALS AND METHODS: We studied muscle biopsy samples from seven patients affected by FM; samples from five patients each with PM and dermatomyositis were studied as disease controls. RESULTS: MMP2 immunoreactivity was present in PM and dermatomyositis, MMP7 only in PM, and MMP9 in PM, dermatomyositis and FM. CONCLUSIONS: Our results confirm that increased MMP9 immunoreactivity in muscle fibres is a common feature of all inflammatory myopathies and suggest that MMP2 and MMP7 cannot be implicated in the inflammatory events of FM.

Adult↗
PubMed2005

Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature.

Thromboembolic events are a serious complication of assisted conception treatment. Thrombosis may be either arterial or venous but the latter is far more common. This phenomenon is more frequent in the lower limb, but several cases of upper extremity thrombosis have been described in the literature. Although the aetiology of these thromboembolic disorders is not fully understood, the mechanism is thought to be due to a hypercoagulable state associated with haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism, ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis that developed in a patient following successful assisted conception in the absence of evident risk factors. In the current literature, the site of thrombosis, possible predisposing factors, oestrogen levels, number of foetuses, maternal and foetal outcomes, and management of thrombosis were analysed.

Adult↗
PubMed2003

Sevoflurane analgesia in obstetrics: a pilot study.

Continuous and intermittent administration of inhalational anesthetics has been successfully employed for treating pain during labor. We conjectured that intermittent sevoflurane administration would be effective for pain relief during labor without side effects to the mother or fetus. Fifty parturients breathed a mixture of 2-3% sevoflurane, oxygen and air before each uterine contraction began. The patients assessed the quality of analgesia by using a visual analogue scale (0-10) before the administration of sevoflurane and after each uterine contraction. All parturients but one were satisfied, demonstrating a mean visual analogue score before and after sevoflurane administration of 8.7 +/- 1.1 and 3.3 +/- 1.5, respectively. Apgar scores at 1 and 5 min were 9 (range 5-9) and 10 (range 8-10), respectively. Our findings suggest that sevoflurane could be effective for the treatment of labor pain.

Journal Article↗
PubMed2003

Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population.

Dysferlin, the protein product of the dysferlin gene (DYSF), has been shown to have a role in calcium-induced membrane fusion and repair. Dysferlin is absent or drastically reduced in patients with the following autosomal recessive disorders: limb-girdle muscular dystrophy type 2B (LGMD-2B), Miyoshi myopathy (MM) and distal anterior compartment myopathy. To date, less than 45 mutations have been described in DYSF and a wide inter- and intra-familial variation in clinical phenotype has been associated with the same mutation. This observation underlines the relevance of any new report describing genotype/phenotype correlations in dysferlinopathic patient and families. Here we present the results of clinical, biochemical and genetic analysis performed on one MM and three LGMD Italian families. By screening the entire coding region of DYSF, we identified three novel mutations (two missense substitutions and one frame shift microdeletion). The possible existence of a founder effect for the Arg959Trp mutation in the Italian population is discussed.

Adult↗
PubMed2002

Limb-girdle myasthenia: clinical, electrophysiological and morphological features in familial and autoimmune cases.

Limb-girdle myasthenia is an uncommon disease and includes familial and autoimmune forms. Patients present proximal muscle weakness and wasting, and sometimes fatigability, without cranial nerve involvement and fluctuations. We observed, during a 15-year period, nine subjects with limb-girdle myasthenia, (24-55 years; 8 males, 1 female) who constituted 3.2% of 281 myasthenic patients attending our department. All had previously received a diagnosis different from myasthenia. Diagnosis of limb-girdle myasthenia was established by clinical, muscle biopsy and electrophysiological assessment including repetitive nerve stimulation and single fiber electromyography. Five patients had the familial form with tubular aggregates in skeletal muscle; four patients had the autoimmune form. Patients with the familial form had a good response to acetylcholinesterase inhibitors, and the patients with the autoimmune form responded to immunotherapy. Our findings reinforce the opportunity to suspect limb-girdle myasthenia in unclassifiable proximal myopathies and to differentiate familial from autoimmune cases, especially for therapeutic implications.

Action Potentials↗
PubMed2001

Complete transposition of the great arteries: patterns of congenital heart disease in familial precurrence.

BACKGROUND: Transposition of the great arteries (TGA) is considered to be associated only rarely with genetic syndromes and to have a low risk of precurrence among relatives of affected patients. Because most family studies have involved a relatively small number of patients and evaluated all types of TGA as a single group, we performed a large, prospective study investigating the precurrence of congenital heart disease in families of children with complete, nonsyndromic TGA. METHODS AND RESULTS: From January 1997 through December 2000, 370 patients with nonsyndromic, complete TGA were consecutively evaluated and enrolled in the study. The occurrence of cardiac and noncardiac anomalies among relatives of the probands was investigated. Relatives with congenital heart disease were found in 37 of 370 families (10%), including 5 of 37 families (13.5%) with more than one affected relative. TGA itself was the most common precurrent malformation: complete TGA occurred in 6 families and congenitally corrected TGA occurred in 5 families. Precurrence risks for congenital heart disease were calculated at 1.8% (8 of 436) for siblings, 0.5% (4 of 740) for parents, 0.5% (16 of 3261) for first cousins, 0.2% (4 of 2101) for uncles/aunts, and 0.06% (1 of 1480) for grandparents. CONCLUSIONS: The present study shows that TGA is not always sporadic in families. Precurrence of concordant cardiac defects within affected family members supports monogenic or oligogenic inheritance of TGA in certain kindreds. Moreover, the occurrence of complete TGA and congenitally corrected TGA among first-degree relatives in several different families strongly suggests an underlying pathogenetic link between these 2 malformations that has been previously unrecognized.

Adolescent↗
PubMed2001

Congenital heart defects in Kabuki syndrome.

Kabuki makeup (Niikawa-Kuroki) syndrome (KS) is characterized by distinct facial anomalies, mental retardation, congenital heart defect (CHD), and skeletal malformations. In the present study we analyze cardiac characteristics and differences in sex prevalence of specific CHDs in our series of patients with KS and review published reports from the literature. Between January 1992 and February 2000, 60 patients (37 males and 23 females) with KS underwent phenotypic and cardiac evaluations at our hospital. CHD was diagnosed in 35 (58%) of our patients. Aortic coarctation (COA) (23%), atrial septal defect (ASD) (20%), and ventricular septal defect (VSD) (17%) were the most frequent CHDs in our series and in previous reports from the literature. Male preponderance was noted in patients with COA. In conclusion, CHD is a cardinal feature of KS. There is an overlap between cardiac malformations of KS and those of Turner syndrome. Male preponderance in patients with KS and COA supports the hypothesis that genes located on the X chromosome may be involved in determining KS in some patients. The high prevalence of CHD prompts accurate re-examination of patients evaluated by pediatric cardiologists in order to identify mild and still unrecognized cases of KS.

Abnormalities, Multiple↗
PubMed2001

Peripheral neuropathy as the presenting feature of multiple system atrophy.

The authors report a case of multiple system atrophy (MSA) with an onset as a peripheral nerve involvement. Their patient, a 55-year-old man, had a 3-year history of distal weakness and atrophy in upper limbs with dysesthesia in the feet. Other identifiable causes of peripheral neuropathy were ruled out. The authors postulate that peripheral nervous system impairment can anticipate the typical appearance of MSA, and they suggest that, in peripheral neuropathies with autonomic system dysfunction, after excluding main causes of autonomic neuropathy, MSA may need to be suspected.

Autonomic Nervous System↗
PubMed2001

Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation.

Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80% of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defects. Abnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow "protected" against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling.

Adolescent↗
PubMed2001

Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.

The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein, Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.

Amino Acid Sequence↗