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L Fiori

Publications and source records attributed to L Fiori.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency.

The oral loading test with tetrahydrobiopterin (BH(4)) is used to discriminate between variants of hyperphenylalaninaemia and to detect BH(4)-responsive patients. The outcome of the loading test depends on the genotype, dosage of BH(4), and BH(4) pharmacokinetics. A total of 71 patients with hyperphenylalaninaemia (mild to classic) were challenged with BH(4) (20 mg/kg) according to different protocols (1 x 20 mg or 2 x 20 mg) and blood BH(4) concentrations were measured in dried blood spots at different time points (T(0), T(2), T(4), T(8), T(12), T(24), T(32) and T(48 h)). Maximal BH(4) concentrations (median 22.69 nmol/g Hb) were measured 4 h after BH(4) administration in 63 out of 71 patients. Eight patients presented with maximal BH(4) concentrations approximately 44% higher at 8 h than at 4 h. After 24 h, BH(4) blood concentrations dropped to 11% of maximal values. This profile was similar using different protocols. The following pharmacokinetic parameters were calculated for BH(4) in blood: t (max) = 4 h, AUC (T(0-32)) = 370 nmol x h/g Hb, and t (1/2) for absorption (1.1 h), distribution (2.5 h), and elimination (46.0 h) phases. Maximal BH(4) blood concentrations were not significantly lower in non-responders and there was no correlation between blood concentrations and responsiveness. Of mild PKU patients, 97% responded to BH(4) administration, while one was found to be a non-responder. Only 10/19 patients (53%) with Phe concentrations of 600-1200 mumol/L responded to BH(4) administration, and of the patients with the severe classical phenotype (blood Phe > 1200 mumol/L) only 4 out of 17 patient responded. An additional 36 patients with mild hyperphenylalaninaemia (HPA) who underwent the combined loading test with Phe+BH(4) were all responders. Slow responders and non-responders were found in all groups of HPA.

Administration, Oral↗
PubMed2004

The headache in the Emergency Department.

The headache is a very frequent symptom and represents the 0.36%-2.5% of all reasons of claim to Emergency Department. Even if it is rarely related to high risk diseases, it is mandatory to promptly differentiate life-threatening conditions. In order to establish a correct diagnostic and therapeutic pathway and ask for aimed specialistic consultation, the emergency physician must be familiar with the various categories of headache. It is important to distinguish between essential headache and secondary headache. All patients presenting to the emergency department with the complaint of headache should be interviewed carefully regarding their history. The quality of pain associated with the intensity, location, rate, duration, modality of onset, relieving or worsening conditions, response to drugs, symptoms or signs associated must be investigated as well. Careful neurological examination including the vision of fundus oculi and the evaluation of rigor nucalis can provide further important diagnostic information. Laboratory exams do not usually give significant issues in the majority of patients with headache. However, dosage of inflammation index can be useful when an infective or inflammatory disease is suspected. CT scan can rule-out the suspicion of organic intracranial causes. When the physician suspects meningitis or subarachnoid hemorrhage (SAH) not showed by CT scanning, rachicentesis can turn out diagnostic. The modality of onset, clinical characteristics and differential diagnosis of subarachnoid hemorrhage, intracranial hypertension, colloidal cyst of the third ventricle, trigeminal neuralgia, temporal arteritis and pituitary adenomas and apoplexy will be discussed. These diseases are not only of neurological and neurosurgical interest, but involve also the physician in the Emergency Department.

Adenoma↗
PubMed2004

Body mass index rebound and overweight at 8 years of age in hyperphenylalaninaemic children.

AIM: To evaluate whether the age at body mass index (BMI) rebound may be associated with overweight at age 8 y in hyperphenylalaninaemic (HPA) children. METHODS: A longitudinal observational study including 97 HPA children born 1984-1993 and detected by the National Neonatal Screening programme. Children were followed up at the same institution and evaluated for dietary intakes and anthropometrical parameters from diagnosis up to the age of 8 y. Outcome measure was overweight at age 8 y, defined according to the International Obesity Task Force. The age at BMI rebound, BMI before and at rebound were considered as potential determinants. Familial overweight, breastfeeding and macronutrients intake at age 1 y were considered as confounders. RESULTS: Mean (95% confidence interval [CI]) age at BMI rebound was 5.0 (4.7-5.3) y. At the age of 8 y, 24.7% (95% CI 16.3-33.1%) of children was overweight. Children overweight at the age of 8 y exhibited earlier BMI rebound than non-overweight children (mean difference [95% CI] -2.1 [-2.8 to - 1.4] y) and higher BMI from the age of 1 y (mean difference [95% CI] 1.2 [0.9-2.5] kg/ m2) onward. Overweight was more likely in children with, rather than without, parental overweight (41.0% vs 19.8%). After adjustment for confounders, logistic analysis showed that earlier BMI rebound (odds ratio [OR] 2.4, 95% CI 1.2-4.8) and BMI at age I y (OR 2.3, 95%CI 1.1-4.98) were independently associated with overweight at the age of 8 y. CONCLUSION: Within the population of this study, overweight at age 8 y was positively associated with early BMI rebound and BMI at age 1 y.

Anthropometry↗
PubMed2003

Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children.

Blood fatty acid status and visual function of 20 treated hyperphenylalaninemic (HPA) children, randomly allocated into two groups to receive supplementation of either long chain polyunsaturated fatty acids (LCPUFA), including docosahexaenoic acid (DHA), or placebo for 12 months, have been investigated three years after the end of the treatment. Although in the LCPUFA group blood DHA levels and P100 wave latency improved at the end of supplementation, they had returned to baseline after three years.

Adolescent↗
PubMed2002

Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area.

Deficiency of amylo-1,6-glucosidase, 4-alpha-glucanotransferase enzyme (AGL or glycogen debrancher enzyme) is responsible for glycogen storage disease type III, a rare autosomal recessive disorder of glycogen metabolism. The AGL gene is located on chromosome 1p21, and contains 35 exons translated in a monomeric protein product. The disease has recognized clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different subjects. The clinical manifestations of GSD III are represented by hepatomegaly, hypoglycemia, hyperlipidemia, short stature and, in a number of subjects, cardiomyopathy and myopathy. In this article, we discuss the genotypic-phenotypic heterogeneity of GSD III by the molecular characterization of mutations responsible for the disease on a collection of 18 independent alleles from the Mediterranean area. We identified by heteroduplex band shift, DNA direct sequencing, and restriction analysis, seven novel mutations (four nonsense point-mutations: R34X, S530X, R1218X, W1398X; two microinsertions: 1072insT and 4724insAA; and one bp deletion: 676DeltaG), together with two new cases carrying a IVS21 + 1 G --> A splicing site mutation previously described in Italian patients. Altogether, 15 alleles were characterized. The correlation between type of mutation and clinical severity was studied in six patients in whom both mutated alleles were detected. Our data confirm the extreme genetic heterogeneity of this disease, thus precluding a strategy of mutation finding based on screening of recurrent common mutations.

Adolescent↗
PubMed2002

Phenylalanine hydroxylase mutations and phenylalanine-tyrosine metabolism in heterozygotes for phenylalanine hydroxylase deficiency.

UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Parents of patients affected by PAH deficiency (n = 25) detected through the Italian Neonatal Screening Program and referred from January 1994 to June 2000, and parents of healthy children were investigated. In total, 68 subjects without any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and gender-matched controls, were recruited. Plasma concentrations of Phe and Tyr in fasting and semifasting (1600 mg Phe oral load) conditions were the main outcome measures. DNA analysis for PAH mutations was performed in all 68 subjects. Compared with controls, heterozygotes showed higher fasting and semifasting Phe concentrations (p < 0.0001), lower semifasting Tyr concentrations (p = 0.015), lower Tyr variations (p = 0.003) and a higher Phe/Tyr ratio (p < 0.0001) in switching from fasting to semifasting conditions. Heterozygotes carrying a severe mutation showed semifasting plasma Tyr concentrations lower than controls (p = 0.019) but not significantly different from Tyr levels found in non-severe carriers (p = 0.197). The Tyr variations were minor in severe carriers than controls (p < 0.001) and non-severe carriers too, although with lower significance (p = 0.089). In six carriers of A403V mutation, parents of mild hyperphenylalaninaemics on an unrestricted diet, significant differences in variations from fasting to semifasting conditions were found compared with parents of patients on a diet. CONCLUSION: Although the great heterogeneity of PAH mutations limits any general conclusion, the results suggest that monitoring plasma Tyr variations may be more sensitive than plasma Phe in assessing the severity of PAH mutations in HPA heterozygotes.

Adult↗
PubMed2001

Sonographic findings in type I glycogen storage disease.

PURPOSE: The aim of this study was to document the sonographic appearance and dimensions of the liver and spleen in patients affected by type I glycogen storage disease and to correlate those findings with laboratory data to evaluate the potential role of sonography in diagnosing that disease. METHODS: Fourteen patients (age range, 3-26 years; 10 patients younger than 18 years) with type I glycogen storage disease proved by liver biopsy were studied prospectively with gray-scale sonography, color Doppler sonography, and spectral analysis. The liver, kidneys, spleen, portal system, hepatic veins, and hepatic arteries were evaluated. Laboratory data were correlated with sonographic findings. RESULTS: In 13 (93%), of 14 patients, the liver was enlarged, and in 11 patients (79%), hepatic echogenicity was increased. In 9 patients (64%), both kidneys were enlarged, and in 6 cases (43%), the spleen was enlarged. In all patients, flow in the portal, splenic, and superior mesenteric veins was hepatopetal, and flow in the hepatic veins was triphasic. In 5 patients (36%), both triglyceride and total cholesterol levels were higher than normal. No focal hepatic lesions were identified. Analysis found no significant association between sonographic findings and laboratory data. CONCLUSIONS: The most frequent sonographic findings in patients with type I glycogen storage disease were hepatomegaly, increased hepatic echogenicity, and enlarged kidneys. Sonography may help in the diagnosis of type I glycogen storage disease, but a liver biopsy is required for a definitive diagnosis.

Adolescent↗
PubMed2001

Stenting of atherosclerotic stenoses of the extracranial carotid artery.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) and stenting seems to be, at present, the treatment of choice for early restenosis after endarterectomy and for atherosclerotic stenoses of supra-aortic trunks near or at the ostium. In contrast, the role of PTA and stenting for treatment of symptomatic and asymptomatic atherosclerotic stenosis of carotid bifurcation is still debated. METHODS: The present study comprises 27 consecutive cases of atherosclerotic lesions of the carotid bifurcation treated with PTA and stenting. All patients were symptomatic, except for 2 suffering from asymptomatic stenosis with contralateral carotid occlusion. There were 23 stenoses occluding 70% or more of the lumen according to the NASCET criteria and 4 mild stenoses (50-60% of the lumen) with large type C ulcers. Criteria for exclusion from surgery in these cases were aged >79 years, previous neck surgery for laryngeal cancer, carotid bifurcation at C2, association with intracranial aneurysms, occlusion of the contralateral carotid artery, and heart, lung and kidney diseases. All procedures were performed under local anaesthesia associated with mild sedation in a few cases. In all cases, self-expandable stents (Wallstent) were used. Follow-up ranged from 6 to 37 months. FINDINGS: Transient neurological deficit occurred in 3 cases (11%). One case (3.7%) experienced a minor stroke at three months. Asymptomatic tight restenosis due to intimal hyperplasia occurred in one case (3.7%). In 8 cases (40%) of complex stenosis involving common and internal carotid arteries there was some loss of contact of the stent with the wall of the common carotid artery in the late follow-up. One case (3.7%) experienced severe and prolonged hypotension and bradycardia during the release of the stent. INTERPRETATION: From literature data and our results it emerges that periprocedural catastrophic embolism is unlikely to occur. The best results are undoubtedly obtained when treating stenosis limited to the internal carotid artery. Nevertheless, the ideal stent to treat vessels of different calibre, as occurs at the carotid bifurcation, is not yet available. The problem of periprocedural cerebral protection has not been resolved. Reported series are heterogeneous and retrospective, and an adequate follow-up of cases is still lacking.

Adult↗
PubMed1999

Surgery and stenting As combined treatment of a symptomatic tandem stenosis of the carotid artery.

International co-operative studies have demonstrated a benefit from surgery for symptomatic and asymptomatic patients affected by internal carotid artery stenosis of 60-70%. The presence of a tandem lesion, intracranial or extracranial, may annul the benefit of surgery. Such patients may thus represent a challenging problem for management if age, good general conditions and a normal neurological status favour a therapy. A 54-year-old man developed transient ischaemic attacks of the left hemisphere; his general condition was good, and neurological status was normal. Angiography showed a tight stenosis at the left common carotid artery near the ostium and at the homolateral carotid bifurcation. At first, a self-expanding wall stent was placed at the level of the common carotid artery stenosis, and immediately after a standard endarterectomy under general anaesthesia was performed. The postoperative course was normal and was complicated only by the presence of a mild deficit of the hypoglossal nerve due to the presence of a high bifurcation. The early and late outcome of our case suggests that stenosis of the proximal common carotid artery may be successfully treated by stenting. While awaiting additional data about this new technology, endovascular techniques and surgery may be complementary in the management of patients suffering from such tandem lesions.

Angioplasty, Balloon↗
PubMed1999

Should genetic analysis in newborn screening and a heterozygote test for hyperphenylalaninaemia be recommended? An Italian study.

OBJECTIVE: To determine whether the introduction of genetic analysis for phenylalanine hydroxylase (PAH) deficiency into regional screening programmes can be supported by the benefit-cost ratio. METHOD: Tests for the genetic PAH locus were carried out in 151 patients with hyperphenylalaninaemia originally from all of the Italian regions. PAH mutations were identified by extraction of genomic DNA from leucocytes (whole blood in EDTA), PAH exon amplification was determined by polymerase chain reaction, restriction enzyme analysis was carried out for some recognised mutations, and DNA sequence analysis for the other mutations. RESULTS: It was found that the eight most common mutations in the population accounted for 49% of the mutant alleles, which is well below the required standard for effective population screening (90%). CONCLUSIONS: Genetic screening for PAH deficiency in Italy does not increase the sensitivity of the methodology and the benefit-cost ratio, and thus provides no advantage, particularly as the correlation between genotype and the metabolic phenotype needed to optimise dietary intervention is still being studied.

Amino Acid Substitution↗
PubMed1998

[Cerebral blood flow in subarachnoid hemorrhage].

Cerebral blood flow (CBF) following subarachnoid haemorrhage varies according to the time of sampling, with regard to the time of bleeding, to clinical conditions of patients and to any possible occurrence of vasospasm. CBF is proportionally reduced upon clinical conditions, involves the totality of patients and represents a diffuse bilateral phenomenon, not dependent on the location of the aneurysm. Following events, such as vasospasm, may deteriorate haemodynamic conditions, especially when unstable. Thus, CBF monitoring is necessary and useful in these patients. The evaluation of this parameter, according to the metabolic demands, appears rather fundamental. Besides, during the first two weeks, all the available therapeutic strategies have to employed in order to achieve the best optimization of the CBF so as to avoid the occurrence or at least minimising the extent of ischemic cerebral lesions.

Cerebrovascular Circulation↗
PubMed1998

[Surgical versus endovascular treatment in cerebral aneurysm. The opinion of a neurosurgeon].

The high risk of rebleeding of ruptured aneurysms imposes the need of their early exclusion from arterial circulation. The onset of endovascular technique of embolization gives a new chance, making, time by time, necessary the choice for the best treatment. The advantages and limits of surgical option are well known and consolidated. The results of endovascular technique are similar in the acute phase, but it lacks an adequate follow up and a clear definition of some technical knowledges. Clinical and anatomical data and a serious analysis of specific technical difficulties of both methods must condition the choice of treatment. Present experience allows us to give sure indications only for certain cases, whereas final landmarks are indisposable in many other situations. However, the team discussion between the neurosurgeon, the neuroradiologist and the neuroreanimator must be the crucial point of the decisional way in every single case.

Embolization, Therapeutic↗
PubMed1998

Dissecting vertebral aneurysm. Report of a case.

Aneurysms of the vertebral artery (VA) are relatively uncommon, accounting for less than 0.5-3.0% of all aneurysms and 20% of aneurysms originating in the posterior fossa. There are three distinct forms of aneurysms: saccular, fusiform and dissecting. The diagnosis of dissecting aneurysm is based on the findings of angiography, surgery and autopsy. Irregular fusiform appearance, intramural retention of contrast medium in the venous phase and alternating irregular stenotic and dilated segment (string and pearl sign) are the basal angiographic findings. Patients with dissection of VA often develop subarachnoid hemorrhages (SAHs), with the typical neck pain or suffer cerebral ischemia. Because of the high risk of rebleeding of dissecting aneurysms, they should be treated as soon as possible, with occlusion of the VA. Nowadays, both surgical and endovascular procedures allow the treatment of dissecting vertebral aneurysms. Anyway, one should be aware that vertebral occlusion performed proximal to PICA origin may be followed by ischemic complications. In this paper, we discuss the diagnostic and therapeutic difficulties associated with dissecting vertebral aneurysms on the basis of personal observation and a review of the literature.

Aortic Dissection↗
PubMed1997

Combined transcranial Doppler and electrophysiologic monitoring for carotid endarterectomy.

The results of carotid endarterectomy can be improved by reducing the perioperative embolic and hemodynamic risks. Electrophysiologic monitoring, although reliable, cannot provide full information. In this study, we report on the combined use of transcranial Doppler (TCD) and electrophysiologic monitoring in 153 patients undergoing 166 carotid endarterectomy procedures. TCD monitoring confirmed the low incidence of intolerance to cross-clamp (1.8%), showing a good correlation with electrophysiologic monitoring. In addition, it frequently showed embolic signals immediately after clamp release, but never during carotid dissection or in the final operative phases. Furthermore, TCD allowed the detection of hyperperfusional flow patterns in four cases, making immediate and aggressive control of arterial pressure possible.

Aged↗
PubMed1997

Incidence of asymptomatic berry aneurysms among patients undergoing carotid endarterectomy.

BACKGROUND: Scattered reports of literature suggest the hypothesis that patients suffering from a severe stenosis of extracranial carotid artery may present an increased rate of intracranial berry aneurysms caused by the hemodynamic stress on the side opposite to the stenosis, namely on physiological shunts. However, this hypothesis has never been verified upon a large and homogeneous series focused on the argument. MATERIALS AND METHODS: We reviewed a consecutive series of 405 patients submitted to carotid endarterectomy for stenosis greater or equal to 70%. RESULTS: Thirteen aneurysm were found in 11 patients (2.6%). Our patients showed a slight increase of incidence regards to general population (1%), maybe due to the large number of aged patients among our subpopulation. Preoperative TCD evaluation showed the presence of increased flow velocities in the physiological shunts, namely the anterior cerebral artery and the anterior communicating artery, in 65% of the patients, and angiography confirmed the redistribution of intracranial circulation. Nevertheless, according to aneurysm location, no statistically significant correlation (0.3 < p < 0.4) was found between the presence of an aneurysm and the values of velocity in these arteries. CONCLUSIONS: As regards the etiology of berry aneurysms, these data suggest that increased hemodynamic stress per se is not sufficient to cause the origin of berry aneurysms. Maybe, a role is possible only if either congenital, or acquired and age-related factor, peculiar of cerebral arteries, coexist.

Aged↗
PubMed1996

Management of symptomatic carotid stenoses with coincidental intracranial aneurysms.

There are at present strong indications for surgery in patients suffering from symptomatic extracranial carotid stenoses of > 70%. Surgery of coincidental aneurysms is a still debated problem, but there is general agreement that it is indicated in selected cases according to the patient's life-expectancy and size and site of the aneurysm. The coexistence of these two lesions raises a decision-making problem. We reviewed 389 endarterectomies and found 12 intracranial berry aneurysms in 10 (2.6%) patients. All the 10 patients were harbouring a symptomatic carotid stenosis of > 70%. Since the correction of a stenosis increases blood flow to an aneurysm, our approach was to first operate on the intracranial lesion and then the stenosis in 7 patients harbouring aneurysms > 5 mm. Two patients affected by small aneurysms < 5 mm of an A2 azygos and left internal carotid artery underwent left endarterectomy only. The last patient was submitted first to percutaneous angioplasty of a left stenosis, then to open surgery of a contralateral middle cerebral aneurysm and finally to intravascular occlusion of a small aneurysm of the left internal carotid bifurcation by menas of a coil; this policy was adopted in order to restore normal haemodynamic conditions before the intracranial procedure. There was no mortality or permanent morbidity following surgery for aneurysm or endarterectomy. Transient morbidity occurred in 2 cases after clipping of aneurysms of the anterior communicating and middle cerebral arteries. Our results suggest that surgery of coincidental aneurysms may give good results even when there is a severe symptomatic stenosis in the neck. Moreover, the presence of a small intracranial aneurysm does not seem to be an additional risk factor for endarterectomy. When the lesions are on different sides, it may be better to treat the stenosis first if it decreases the ipsilateral cerebral blood flow.

Aged↗