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Biomedical subjects

S Savasta

Publications and source records attributed to S Savasta.

At least 19 recordsLinked to original sources
PubMed2007

Topiramate in frontal lobe epilepsy.

BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult to treat and there are few studies about the use of topiramate (TPM). AIM OF THE STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE. METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was administered as a first drug (n = 16) or converted after previous treatment (n = 39). All patients were followed every 3 months for at least 1 year. The patients were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to-treat' patients. RESULTS: Overall, all patients completed the 1-year study. At the end of follow-up, 10 patients showed disappearance of seizures and 33 patients showed improvement in seizure frequency. In particular, among the newly diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16 patients showed very good response; in the other group, 4/39 patients showed complete cessation and 4/39 patients showed a very good response. No patients of both groups had worsening of seizures. No treatment-limiting adverse events associated with TPM were reported. CONCLUSIONS: TPM is effective in newly diagnosed patients with FLE; TPM can be considered for the treatment of FLE.

Adolescent↗
PubMed2002

Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy.

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.

Adolescent↗
PubMed2001

FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts.

We describe the case of a 15-year-old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21-22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI-7732 and WI-607, with WI-7396 and WI-8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis.

Abnormalities, Multiple↗
PubMed2001

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

Acanthosis Nigricans↗
PubMed2001

Symptomatic unilateral renal angiomyolipoma in a child with tuberous sclerosis.

We report a case of unilateral renal angiomyolipoma in a 10-year-old boy with tuberous sclerosis. The case is worthy of attention because the symptoms occurred at an early age and because the lesion was unilateral, the latter confirmed at 11-year follow-up. The presentation and treatment are discussed, and the pertinent literature is reviewed. The case demonstrates that it is of clinical importance to monitor renal involvement in children with tuberous sclerosis.

Angiomyolipoma↗
PubMed2001

Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency.

Three cases of Leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.

Acidosis, Lactic↗
PubMed1999

Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS).

The kinesin-related protein (HSET) gene belongs to the kinesin superfamily, the members of which are involved in cellular transport processes. The HSET gene product was previously characterized by partial cDNA sequencing. The gene is located on the short arm of human Chromosome 6 (6p21.3), at the centromeric end of the major histocompatibility complex. Here, we report the genomic structure of the complete HSET gene together with its flanking loci. Sequence analysis of the 40 kilobase (kb) cosmid clone containing the HSET gene also revealed the presence of several new genes not related to the kinesin superfamily. These include a 60S ribosomal protein L35A-like pseudogene (rPL35A-like) on the telomeric side and a polycomb-like gene (PHF1), a copper tolerance-like gene (CUTA1) and the 5' part of the synaptic ras-GTPase-activating protein (SynGAP) gene centromeric of HSET. In addition, a complete 60S ribosomal protein L12-like (rPL12L) gene in intron 3 of the HSET gene was identified which appears to have an open reading frame. The possible involvement of the HSET gene and a beta-tubulin gene (TUBB) in the pathogenesis of immotile cilia syndrome (ICS) was studied by screening two unrelated ICS families with microtubular defects and suspected HLA linkage for mutations within the HSET gene and the TUBB gene. Four single base substitutions were detected in the HSET gene, and none in the TUBB gene. On the basis of these data, a role of the HSET and TUBB products in the pathogenesis of ICS in the two families is unlikely.

Amino Acid Sequence↗
PubMed1996

Cardiovascular reflex changes preceding episodes of vasovagal syncope in paediatric subjects.

1. The cardiovascular reflex changes preceding episodes of vasovagal syncope (VVS) in paediatric age were investigated in 12 subjects and in 20 controls, supine and upright, by spectral analysis of RR interval, respiration, systolic and diastolic blood pressure. 2. The sympatho-vagal control on the heart and blood pressure was assessed by the power of the low- (LF: index of sympathetic activity) and high-frequency oscillations (index of vagal activity to the heart). 3. In VVS group the supine blood pressure was lower than in controls and fell after tilt, while remained unchanged in controls. The blood pressure LF increased in control group during early and prolonged orthostasis, whereas in the VVS group the LF tended to decrease after early orthostasis and were not significantly greater than supine before VVS. 4. In the VVS group the sympathetic control of blood pressure appears reduced or ineffective, and progressively worsens before the VVS episode.

Adolescent↗
PubMed1996

Pyruvate dehydrogenase deficiency in a child responsive to thiamine treatment.

We report the clinical features in a 4-year-old child who was investigated for a suspected metabolic disorder but was subsequently diagnosed as having a pyruvate dehydrogenase deficiency. A muscle biopsy was performed and the data obtained suggested thiamine treatment which resulted in a regression of the clinical findings and a return to normal values of blood lactic and pyruvic acids. The interruption of thiamine supplementation after 1 year of treatment led to a prompt recurrence of the previous clinical and biochemical symptoms.

Biopsy↗
PubMed1996

Pulmonary changes in a man affected by von Recklinghausen's disease.

Lung involvement in von Recklinghausen's disease is very rare and only sporadic cases have been reported in the literature. We present the case of a man affected by neurofibromatosis type 1 (NF1). The man complained of shortness of breath of 3-4 years duration. Chest radiograph and computed tomographic (CT) scan showed the presence of severe bullous emphysema, with extensive widespread bulky subpleural bullae, involving mainly the upper lobes and apical segments of the lower lobes, bilaterally. Functional respiratory tests documented a picture of severe obstruction associated with marked alveolar hyperinflation (vital capacity (VC) 80% of predicted, forced expiratory volume in one second (FEV1) 49% pred, maximal mid-expiratory flow (MMEF) 22% pred, residual volume (RV) 151% pred). Capillary alveolar diffusion was also markedly altered (transfer factor of the lungs for carbon monoxide (TL,co) 41% pred). The eventual prospect of a lung transplant, never previously considered for this disease, has been advised by the thoracic surgeons. In the light of this possibility, multidisciplinary assessment and monitoring of respiratory function over time are indispensable, in order to identify the transplant window correctly.

Adolescent↗
PubMed1995

Recurrent chest pain as the presenting manifestation of spinal meningioma.

We report the case of a 9-year-old boy with a spinal cord meningioma whose only manifestations were recurrent episodes of chest pain lasting for 2 years. This case shows that spinal cord meningioma should be considered among the possible causative factors of chronic chest pain in childhood.

Chest Pain↗
PubMed1994

The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome.

The product of the human motilin gene (MLN) has an important role in regulating gastrointestinal motility. The precise chromosomal localisation and expression of this gene are still unresolved. Here, we report a detailed study assigning MLN to 6p21.3; MLN is tightly linked to the HLA-DQalpha locus. Moreover, MLN expression has been evaluated in a large series of tissues. Positive signals have been obtained for brain, bronchi and a gastrointestinal malignancy. Direct sequencing exon by exon of the codifying region, intron/exon boundaries and promoter has allowed the identification of three DNA polymorphisms, one of which corresponds to a common protein variant. The chromosomal localisation of MLN, and its expression in broncoepithelial cells suggests that this gene is involved in immotile-cilia syndrome (ICS) disease. Sequence and segregation analysis of the MLN gene carried out in two families, in which the disease locus was previously assigned to 6p21.3, exclude MLN as a candidate gene for the HLA-associated form of ICS.

Base Sequence↗
PubMed1993

Infantile mitochondria encephalomyopathies: report on 4 cases.

Four muscle biopsies from the quadriceps femoris muscle of children with symptoms suggesting mitochondrial encephalomyopathy were examined for morphological and biochemical differences. From a biochemical point of view, our patients showed a derangement of mitochondrial metabolism and in particular a marked deficit in the activity of cytochrome c oxidase. In all patients there was an abnormally high rise of lactate and pyruvic acid levels in blood before and after glucose loading. Results of morphological and enzyme histochemical studies showed smaller muscle fibre diameters than in normal children. Typical red ragged fibres and ultrastructural abnormalities in muscle mitochondria were present in 1 case only. Three patients showed focal changes in the distribution of some sarcoplasmic oxidative enzyme activities. The present findings suggest that the main metabolic disorder, pointed out by biochemical studies, is scarcely reflected by morphological and ultrastructural studies in the early stages of mitochondriopathies.

Biopsy↗