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F Taroni

Publications and source records attributed to F Taroni.

At least 73 records · Page 4Linked to original sources
PubMed1996

Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion.

Hereditary neuropathy with liability to pressure palsies (HNPP) is commonly associated with a 1.5-megabase deletion on chromosome 17p11.2-12. We analyzed the phenotypic expression of the deletion in 39 HNPP patients from 16 families carrying the deletion. Two-thirds of the individuals had episodes of acute mononeuropathy, often involving nerve territories of the upper limbs or brachial plexus; however, 41% of affected subjects were unaware of their disease, and 25% were almost or totally free of symptoms; one-third complained of chronic symptoms and four older patients had a picture of polyneuropathy. Electrophysiologic abnormalities differed among affected subjects, ranging from conduction abnormalities localized at common entrapment sites to diffuse conduction slowing, usually more evident at entrapment sites; patients from one family had preeminent proximal involvement. The spectrum of phenotypic expression of deletion-associated HNPP appears to be broader than previously thought. The prevalence of the disease is probably underestimated, and the availability of molecular diagnosis should increase disease detection.

Adolescent↗
PubMed1996

Molecular analysis of carnitine palmitoyltransferase II deficiency with hepatocardiomuscular expression.

Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibility of this mutation for the disease. Metabolic consequences of the SER-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, with out consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency.

Base Sequence↗
PubMed1996

[Evaluation of activity in intensive care. A comparison of administrative and epidemiologic data].

This paper reports on results of a formal comparison of data excerpted from 3 different data sources regarding patients cared for in Italian Intensive Care Units (ICU) in 1992. The analysis was carried out in order to assess whether the administrative data routinely collected for reimbursement and policy issues are valid when compared with data from epidemiologic studies. First, using data from the Central Service for Health Planning (SCPS) a general description of the whole national scenario is shown. All the Italian data from 265 Italian hospitals having at least one ICU were analyzed. In these hospitals there were 2,357 ICU beds (4.3 beds/1000 inhabitants, with large regional variability). About 100,000 cases were identified (1% of all the hospital admissions received ICU care at some moment during the stay), with an overall hospital mortality rate of 17%. This estimate was largely different from those obtained from GiViTI data base (5100 patients from a national sample of 114 ICUs), where mortality rates were always higher (25 and 30%, for ICU and hospital mortality). Second, a more detailed analyses and comparison was carried out in the subsample of cases admitted in the Hospitals of the Regione Lombardia. In this case, beside the data from SCPS (No = 20580) and from GiViTI (No = 1121), the Regional data-base formed by all the discharge from 41 hospitals having at least one ICU were available (NO = 16674), allowing a formal comparison between estimates obtained from 3 different sources. In this sub-sample, although administrative data showed a good capability and satisfactory accuracy to describe the volume and socio-demographic and clinical characteristics of the cases when compared with GiViTI estimates, still a systematic underestimate of the overall ICU and hospital mortality was present. Moreover, an unexpected high rate of cases were apparently discharged alive from ICU (16.5 versus 32.6% in GiViTI). Tentative explanations and implications of these phenomena are discussed in the text. Finally, in the Lombardia sub-sample a formal description of the case-mix using the Diagnosis Related Group (DRG) system was carried out in order to identify strengths and limitations of this approach when adopted in the ICU setting. Overall, when data are analyzed according to the kind of Major Diagnostic Category (MDC), 75% of all cases were concentrated in 5 alone, with very peculiar concentration in some specific categories. For example, 45% of all the hospital admissions related to the multiple trauma were actually admitted in the ICU setting. At DRG level, fifty of the 493 DRGs available explained 65% of all the cases, showing an unexpected capability of this system to detect the ICU case-mix. The most represented surgical DRG was the number 107 (Coronary Arterial Bypass Graft, without catheterization) and the corresponding medical was the 28 (Cerebro Vascular Accident, excluding TIA).

Adolescent↗
PubMed1995

Kennedy's disease: clinical and molecular study of two Italian families.

Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is a rare X-linked motoneuron disorder with variable signs of androgen insensitivity. It is associated with the expansion of a trinucleotide CAG repeat within the androgen receptor (AR) gene. We here report our clinical and molecular findings in two Italian families with Kennedy's disease. The increased size of the CAG repeat was demonstrated in four affected males and seven carrier females.

Aged↗
PubMed1995

The risk of adenomatous polyps in asymptomatic first-degree relatives of persons with colon cancer.

BACKGROUND & AIMS: Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectal neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients. METHODS: The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps. RESULTS: Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps (chi 2 test; P = 0.006; odds ratio, 3.2), In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively (chi 2 test; P = 0.04; odds ratio, 2.9). CONCLUSIONS: Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dysplastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.

Adenomatous Polyposis Coli↗
PubMed1995

Carnitine palmitoyltransferase II deficiency: structure of the gene and characterization of two novel disease-causing mutations.

Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. To facilitate the identification of disease-causing mutations in the CPT II gene (CPT1), we have established the genomic organization of this gene. CPT1 spans approximately 20 kb of 1p32 and is composed of five exons ranging from 81 to 1305 bp. The sequences of the exon--intron boundaries were determined for each exon and conformed to the consensus splice junction sequences. The 5' and 3' untranslated regions in exon 1 and 5, respectively, were also determined, including the polyadenylation signal and the polyadenylation site. The mature transcript is predicted to be 3090 nt in length. CPT1 exons from CPT II-deficient patients were amplified and directly sequenced. Two novel disease-causing mutations were identified and characterized. The first mutation was a C-665-to-A transversion in exon 1 resulting in a proline-to-histidine substitution at residue 50 of the protein (P50H). This amino acid substitution occurs within a leucine-proline motif that is highly conserved in acyltransferases from different species. The mutation was detected in both alleles of patient 05SB of Italian ancestry, and in one allele of patients 11EG, 38PG, and 26FD of Italian, Dutch, and French ancestry, respectively. The second mutation was a rare G-2173-to-A transition in exon 5 causing an aspartic-acid-to-asparagine substitution at amino acid 553 (D553N) and the generation of a new MseI site. The mutation was detected only in one allele of patient 15MB, of Italian ancestry, who was also heterozygous for the common S113L substitution. Transfection experiments in COS cells demonstrated that both mutations drastically depressed the catalytic activity of CPT II. Biochemical characterization of P50H mutant CPT II in cultured cells from patient 05SB showed that the mutation does not affect substrate binding sites. Finally, immunoblot analysis demonstrated that both mutations were associated with markedly reduced steady-state level of the protein, thus indicating decreased stability of the mutant CPT II.

Adult↗
PubMed1994

Identification of 5' regulatory regions of the human carnitine palmitoyltransferase II gene.

We have identified two partially overlapping genomic clones that contain part of the 5' regulatory region of the human carnitine palmitoyltransferase II gene. The 1.2 kb region upstream the transcription start site, as defined by primer extension experiments, shows promoter activity when inserted upstream of a reporter gene and contains a putative insulin responsive element.

Base Sequence↗
PubMed1994

Mitochondrial diseases.

Mitochondrial diseases are heterogeneous and characterized by a primary defect of the mitochondrial energy output. Genetic defects of mitochondrial energy enzymes may be due to either nuclear DNA gene mutations or mitochondrial DNA (mtDNA) mutations. Among hereditary defects of nuclear-encoded mitochondrial enzymes, carnitine palmitoyltransferase II (CPT-II) deficiency and pyruvate dehydrogenase complex (PDHC) deficiency are of major interest to the neurologist. Several mutations in the CPT-II gene as well as in the X-linked E1 alpha subunit gene of PDHC have been reported and associated with different clinical phenotypes. mtDNA-related syndromes include mitochondrial encephalomyopathies (e.g. MELAS, MERRF, NARP, MIMyCa, etc.), 'pure' encephalopathies (e.g. LHON) and a few syndromes involving only non-neurological systems (e.g. Pearson's pancreas-bone marrow syndrome or diabetes mellitus). Three kinds of molecular lesions have been identified in mtDNA-related disorders: point mutations of protein-encoding mtDNA genes (mit- mutations), point mutations of mtDNA-tRNA genes (syn- mutations) and large-scale rearrangements of mtDNA (rho- mutations). Point mutations (mit- and syn+) are usually maternally inherited, while single large-scale mtDNA rearrangements are usually sporadic. Furthermore, mendelian traits leading to either qualitative or quantitative abnormalities of mtDNA (i.e. multiple mtDNA deletions and tissue-specific mtDNA depletion, respectively) are the first examples of genetic dysfunction of nuclear-mitochondrial communication. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non-invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochondrial disorders, a rapidly expanding area of clinical neurology.

DNA, Mitochondrial↗
PubMed1994

[The public-private mix in hospital care in the Lombardy region].

OBJECTIVES: 1) to compare complexity and severity of the case-mix in the public and private sector, overall and across individual hospitals, and to examine their relative efficiency, by contrasting DRG and/or stage specific average length of stay (ALOS); 2) to assess the impact of a new contractual scheme based on a preassigned number of beddays for a restricted list of specific conditions. DATA SOURCES: Discharge data on 940.670 admissions to 101 public hospitals and 185.161 admissions to 55 private hospitals in the Regione Lombardia in 1990, assigned to HCFA-DRGs, 8th version and to stages and substages of principal and unrelated diagnostic categories, based on Disease Staging. RESULT: The spread of the case-mix is higher in the private sector, which also shows a higher concentration of admissions across hospital for specific medical and surgical conditions. The proportion of more advanced stages of disease is higher in the public sector, for most of the most frequent diagnostic categories. Obstetric care, including abortion, is the largest single public sector activity, while it is virtually not existent in the private sector. Elective surgical procedures, including ENT, cataract and varicose veins surgery make up a substantial proportion of the private hospitals' case load. DRGs-specific ALOS is longer in public hospitals for the most frequent surgical DRGs, mainly due to their preoperative LOS. The net impact of the proposed contractual scheme will save substantial proportion of beddays for most of the conditions considered, except cataract and varicose veins surgery.

Adult↗
PubMed1993

[Sexual assault: could the perpetrators not be identified more often?].

Sex crimes represent an important category of crimes. Physicians have to deal with them when treating victims in the emergency room. Forensic scientists, on their side, try to collect any trace of physical contact between victim and aggressor (sperm, fibres, etc.). But their success is largely dependent on the quality of the first intervention. Crucial evidence can be damaged or lost. Collaboration between physician and forensic scientist is essential when dealing with sex crimes to provide victims with the medical care they need, while using every piece of evidence which will allow the identification of the authors.

DNA↗
PubMed1993

Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients.

Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. We have identified a missense mutation (Ser113Leu) in one patient with the classical muscular symptomatology. Transfection experiments in COS cells demonstrate that the mutation drastically depresses the catalytic activity of CPT II. The mutation results in normal synthesis but a markedly reduced steady-state level of the protein, indicating decreased stability of mutant CPT II. The Ser113Leu mutation is the most frequent cause of CPT II deficiency. The mutation can be detected easily by restriction analysis enabling molecular diagnosis of most patients and identification of heterozygous carriers.

Alleles↗