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Biomedical subjects

C Meli

Publications and source records attributed to C Meli.

At least 19 recordsLinked to original sources
PubMed2005

Maternal exposure to the antiepileptic drug vigabatrin affects postnatal development in the rat.

The objective was to investigate, in the rat, the effects of maternal exposure to vigabatrin (VGB) on the postnatal motor-cognitive behaviour of the offspring. We used an experimental evaluator-blind, placebo-controlled study in the rat. Ten pregnant rats were divided into five groups and treated with different doses of VGB (250, 500, 750, 1000 mg/kg/day) or placebo from gestation day (GD) 6 to GD10. After delivery, 56 pups (40 pups prenatally exposed to VGB and 16 pups exposed to placebo) were evaluated for motor-cognitive behaviour throughout postpartum day 40. At the end of testing sessions the animals were sacrificed and brain tissues processed for biochemical analysis of GABA levels. Body weight of pups and young rats whose mothers were treated with a dose of 750 mg/kg/day were significantly lower both at birth and during the whole postnatal life with respect to the control groups. Young rats of this group exhibited impaired performance in both the open-field and water maze tasks. Brain GABA contents were dramatically increased in this group of rats. No other significant nutritional, biochemical or behavioural changes were observed after treatments with doses of VGB lower than 750 mg/kg/day. The exposure to a dose of 1000 mg/kg caused abortion. Maternal exposure to VGB at relatively high doses (750 mg/kg/day) is likely to cause some important changes of the nutritional status during the pre- and postnatal life. Thus, the biochemical and cognitive abnormalities observed in this study could be related to some disturbances of brain development induced by malnutrition and/or to a disturbance of neuronal programming of the gabaergic system.

Animals↗
PubMed2005

Neonatal hypophosphatasia and seizures. A case report.

Hypophosphatasia is a rare genetic disease characterized by deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity, excessive urinary excretion of phosphoethanolamine, poor bone mineralization and skeletal anomalies. The shortage of alkaline phosphatase (ALP) alters the process of mineralization of skeleton causing a reduced transformation of phosphoethanolamine into phosphatidylethanolamine (cerebral phospholipid) with consequent high serum and urinary levels of phosphoethanolamine, a sensitive and highly specific marker for the disease. Four clinical forms have been described based on the age of onset with different courses and prognoses. An unusual case of lethal perinatal hypophosphatasia associated with seizures observed in a newborn admitted to Neonatal Intensive Care Unit of the University of Catania is described.

Chromatography, Ion Exchange↗
PubMed2001

Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The most consistent neurologic finding was spastic paraparesis, seen in five of the eight patients. However, all showed signs of pyramidal tract involvement. A broad spectrum of pathogenetic mutations (including missense, nonsense, splice site, insertion, and deletions) were identified in the ORNT1 gene.

Adolescent↗
PubMed2001

PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis.

The molecular basis of PAH deficiency in the Sicilian population is characterized by a marked heterogeneity, with 44 mutations at a single locus identified by a "gene-scanning" approach and accounting for a detection rate of 91%. The remaining 9% of PAH alleles does not bear mutations in any of the 13 exons and 24 exon/intron junctions. Three mutations IVS10nt-11 G > A, R261Q, and A300S accounted for 30.5%, whereas the remaining mutations were found at relative frequencies of less than 5% and 20 mutations were observed once only. Five mutations have been detected only in Sicilians so far. By studying the association of mutations with intragenic STR-VNTR haplotypes ("minihaplotypes"), "identity by descent" has been established for 24 mutations also detected in other populations. This finding supports the hypothesis of a multipolar origin for a large proportion of PAH mutant alleles currently detected in Sicilians. In order to improve our understanding of the clinical heterogeneity of PAH deficiency in this population, we have for the first time analyzed three missense mutations L41F, T92I, and P211T in vitro by the pCDNA3/COS-7 eukaryotic expression system and found an activity of 10, 76, and 72%, respectively, compared to normal PAH. In two HPA patients with mild PKU and mild hyperphenylalaninemia (MHP), harboring respectively L41F/R261Q and T92I/P281L genotypes, the predicted biochemical effect of these genotypes appeared to be consistent with the metabolic phenotypes. In contrast, discordant metabolic phenotypes (mild PKU and MHP) were observed in two unrelated patients bearing the same R261Q/P211T genotype, a finding which underscores the complex relationship linking genotype to phenotype in PAH deficiency. Hypotheses on the possible mechanisms responsible for the observed discordance are discussed. The spectrum of PAH gene mutations in Sicily reflects the complex demographic history of this island at the crossroad of prehistoric and historical migrations in the Mediterranean sea. The data presented in this study also add to the present knowledge on the relationship between PAH genotypes and HPA phenotype and are expected to improve PAH genotyping among individuals with hyperphenylalaninemia.

Alleles↗
PubMed2000

[A case of carcinoid with multiple sites in the jejunum and distal ileum].

Multiple carcinoid tumors of the small bowel with more than 3 lesions are very unusual. The authors report a case with 4 lesions, 2 of those localized in the jejunum with more advanced infiltration of the wall and extension to regional mesenteric lymph nodes, revealed by ultrasonography. The relative low incidence and particularly the vague, nonspecific clinical presentation, the unusual site in the jejunum, and failure of the radiological examine of one year before lead to not suspect this condition prior to US examination. However, the feature of asymmetric, concentric thickening of the bowel wall requiring a more accurate exam by CT with oral contrast was able to confirm the suspect of the intestinal tumor. The patient, 80 year old, underwent radical surgery with a wide lymph nodes dissection as well as double resection of the jejunum and distal ileum. The post-surgical outcome was uneventful. A 12-month follow-up is free of the disease.

Abdomen↗
PubMed1998

Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia.

This report identifies eight new mutations of the phenylalanine hydroxylase gene detected in Italian patients with hyperphenylalaninemia. The trivial name of the mutations, predicted phenotypic effect, and population of origin (Italian region) are as follows: F55L (nonconservative change: classic, moderate, mild PKU ?; Sicily), IVS2nt-13 (splicing defect, classic PKU; Tuscany), I65N (nonconservative change classic, moderate, mild PKU ?; Sicily), H201Y (non-PKU HPA; Sicily), I269L (non-PKU HPA, or polymorphism; Sicily), IVS7nt3 (splicing defect or polymorphism; Sicily), I283N (classic PKU; Sicily), IVS12nt2 (splicing defect, classic PKU; Sicily and Apulia). In Sicily, the relative frequency of mutations F55L, I65N, H201Y, I269L, IVS7nt3, I283N, IVS12nt2 is < 1%. The seven new mutations identified in the Sicilian population increase the remarkable genetic heterogeneity typical of this population with an estimated homozygosity value at the PAH locus of 0.041.

Adolescent↗
PubMed1998

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.

Alleles↗
PubMed1998

Uterine diffuse adenomatoid tumor. Does it represent a different biological entity?

Adenomatoid tumor represents a type of mesothelioma apparently confined to the genital tract and characterized by its benign behavior. Its morphological aspects are well known and, until now, it has been described as a nodular mass except for a case diffusely infiltrating the entire myometrium in an immunosuppressed patient. We report a case of benign mesothelial tumor characterized by histological, immunophenotypical and ultrastructural features of an otherwise typical adenomatoid tumor but diffusely growing below uterine serosal surface into the myometrium without discernible borders. The existence of a diffuse type of adenomatoid tumor might reflect a different nature of this neoplasm leading to the hypothesis that this variant of benign mesothelioma represents a distinct biological entity.

Adenomatoid Tumor↗
PubMed1997

Comparison between transrectal ultrasonography and computed tomography with rectal inflation of gas in preoperative staging of lower rectal cancer.

Computed tomography with rectal air insufflation was compared with transrectal ultrasonography (TRUS) in 63 patients. The CT protocol involved pre- and postcontrast scans with 5 mm slice thickness following air insufflation in IV antiperistaltic agent. Of the patients, 79 % were scanned in the prone position. Results of the preoperative examinations were compared with the histological findings. The CT examination had an accuracy rate of 74 %, predicting perirectal spread with a sensitivity of 83 % and a specificity of 62 %, whereas the corresponding figures for TRUS were 83, 91 and 67 %. The accuracy, sensitivity and specificity of CT and TRUS for nodal involvement were 57, 56, 57, 66, 68 and 64 %-respectively. These findings confirm that TRUS is more accurate than CT in local tumour (T) staging and in detecting nodal (N) spread. However, the appropriate CT technique shows spread of tumour outside the rectal wall and locoregional lymph nodes with reasonable accuracy. Lymphatic spread correlated with nodal size. TRUS and CT correctly staged only 57 and 43 %, respectively, of cases with nodal metastases with maximum diameter of 5 mm. TRUS sometimes overstaged perirectal growth of tumour in 7 patients, due to inflammation (5 patients) or incorrect positioning of the balloon in relation to the tumour surface (2 patients).

Adult↗
PubMed1996

PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population.

The results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

[Role of computerized tomography following transrectal air insufflation and hypotonization and transrectal ultrasonography in the staging of rectal tumors].

Computed Tomography (CT) with rectal air inflation was compared with transrectal ultrasound (TRUS) in the preoperative staging of lower rectal cancer in 126 patients. Precontrast and postcontrast CT scans were performed with 5 mm thick slices; the rectum was previously inflated with air and antiperistaltic agents were administered. Preoperative results were compared with histologic findings. The accuracy, sensitivity and specificity of CT in predicting perirectal spread were 76%, 62% and 83%, whereas the corresponding figures for TRUS were 84%, 69% and 92%. The accuracy, sensitivity and specificity of CT and TRUS for nodal involvement were 58%, 60%, 57% and 72%, 68% and 66%, respectively. These results show that TRUS predicts perirectal spread and detects nodal metastases better than CT. However CT, when performed appropriately, shows tumor spread into perirectal fat and locoregional lymph nodes with high accuracy. Lymphatic involvement is strictly correlated with tumor size: TRUS and CT correctly staged only 57% and 43%, respectively, of the cases with nodal metastases and max. diameter of 5 mm. TRUS sometimes overstaged perirectal tumor growth (13 patients in our series) due to perirectal inflammation (9 cases) or artifacts caused by the presence of air bubbles between the probe and the tumor surface (4 patients). TRUS is a very useful tool for detecting tumor distance from the anal opening; in our series, the distance was incorrectly calculated only in one case (3 cm with TRUS versus 4 cm at surgery).

Adenocarcinoma↗
PubMed1996

[Nonpalpable lesions of the breast. A new technique of ultrasound-guided excision biopsy].

The authors have developed a simple and accurate technique of excisional biopsy for non-palpable breast nodes using an intraoperative sonographic technique. Identification, localization and exeresis of the lesions are guided by means of a sterilized transducer introduced through the surgical wound. The confirmation of the correct biopsy is evaluated by scanning the specimen gowned with a surgical glove and comparing the intra- and postoperative ultrasonographic images. The results of analysis showed that in all cases the altered area was removed with extreme accuracy and the ultrasonography is reliable in identifying pathological or suspicious areas since the dimensions of the lesion measured with the scanner correspond significantly to the dimensions of the lesions when measured histologically.

Biopsy↗
PubMed1995

Levels of L-asparagine in CSF after intramuscular administration of asparaginase from Erwinia in children with acute lymphoblastic leukemia.

PURPOSE: As part of a study on the pharmacokinetics associated with the administration of asparaginase (ASNase) from Erwinia to the CNS, we determined the levels of asparagine in the CSF of children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twenty children received eight standard doses of intramuscular ASNase (10,000 IU/m2) every 3 days as part of induction therapy. In the postremission phase of therapy, the children were randomized to receive either 20 courses of high-dose intramuscular ASNase (25,000 IU/m2) weekly (n = 8) or four courses of standard-dose intramuscular ASNase (10,000 IU/m2) every 3 days (n = 12). RESULTS: All patients had detectable levels of L-asparagine in the CSF at the time of diagnosis. The levels of L-asparagine in CSF were undetectable in 15 of 20 (75%) and in seven of 19 (36.8%) children 3 and 5 days, respectively, after administration of standard-dose ASNase. After administration of high-dose ASNase, the levels of L-asparagine in the CSF were undetectable in five (62.5%) and two (25%) of eight children after 3 and 5 days, respectively. CONCLUSION: In this study 60% to 70% and 25% to 35% of children had complete depletion of L-asparagine from the CSF after 3 and 5 days, respectively, after administration of both schedules of ASNase from Erwinia. In the remaining patients, administration of ASNase may have resulted in a suboptimal antileukemic effect at the CNS level.

Administration, Oral↗
PubMed1993

[Surgical treatment of non-toxic multinodular goitre. Retrospective evaluation of a personal case series].

The authors base their study on a retrospective evaluation of a personal series of patients and on a review of the literature on this topic. They focus their attention on surgical problems relating to the type of treatment of non-toxic multinodular goitre. On the basis of the data obtained, they underline that in this pathology total thyroidectomy is the most appropriate form of surgery and does not entail a higher morbidity in relation to more conservative resection.

Follow-Up Studies↗