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Biomedical subjects

P Cortelli

Publications and source records attributed to P Cortelli.

At least 127 records · Page 7Linked to original sources
PubMed1993

Defective brain energy metabolism shown by in vivo 31P MR spectroscopy in 28 patients with mitochondrial cytopathies.

We studied brain energy metabolism by phosphorus magnetic resonance spectroscopy (31P MRS) in 28 patients with mitochondrial cytopathies, and 20 normal control subjects. Fourteen patients had myopathy alone, six had only mild brain symptoms, and eight showed different degrees of brain involvement. Brain 31P MRS showed a low phosphocreatine content in all patients, accompanied by a high inorganic phosphate in 14 of 28 patients. The average value of the Pi concentration in the patient group was significantly (p = 0.009) different from the control group. The cytosolic pH was normal. From these data were derived a high concentration of ADP (calculated from the creatine kinase equilibrium), a high percent value of V/Vmax for ATP biosynthesis, and a low phosphorylation potential, all features showing a derangement of brain energy metabolism, in all patients with mitochondrial cytopathies. 31P MRS proved to be sensitive enough to disclose a deficit of mitochondrial functionality not only in the affected patients, but also in those without clinically evident brain symptoms.

Adenosine Diphosphate↗
PubMed1993

Testing models for genetic determination in migraine.

We collected two clinically matched samples of patients, one sample affected by migraine with aura the other by migraine without aura, to investigate the genetic determination of these conditions. A maternal and X-linked transmission for both these diseases was considered unlikely after pedigree analysis. Classical segregation analysis indicated a likely autosomal recessive kind of transmission for both. Reduced penetrance and the h2 values, however, imply the presence of additional genetic and/or environmental factors controlling the phenotypic expression of migraine.

Adolescent↗
PubMed1993

[18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.

We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.

Adult↗
PubMed1993

Pharmacodynamic modeling of oral levodopa: clinical application in Parkinson's disease.

We investigated the relationship between levodopa plasma concentration and the tapping effect, after a standard oral levodopa test, by kinetic-dynamic modeling in 40 parkinsonian patients with stable or fluctuating response to levodopa, and found no difference in levodopa plasma pharmacokinetics between stable and fluctuating patients. Conversely, levodopa equilibration half-life between plasma and effect-site concentration was five-fold shorter on average in fluctuating patients. Overall, levodopa equilibration half-life highly correlated with the duration of tapping response and provided a reliable quantitative index of central mechanisms that affect the length of clinical effect. Individual fitting of tapping measures to modeled drug effect-site concentrations by sigmoid Emax model revealed that fluctuating patients required almost two-fold higher levodopa concentrations (EC50) to elicit almost the same motor response (Emax). These findings suggest that shortening of levodopa clinical effect may be accompanied by a reduced drug affinity for the nigrostriatal dopaminergic system (EC50), with no change in its intrinsic activity (Emax).

Administration, Oral↗
PubMed1992

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism.

Adult↗
PubMed1992

Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor.

"Endozepines" are endogenous ligands for the benzodiazepine recognition sites on gamma-aminobutyric acid A receptors in the nervous system. Idiopathic recurring stupor (IRS) is a syndrome of spontaneous stupor or coma that is not associated with known metabolic, toxic, or structural abnormalities but can be reversed by flumazenil, a pure benzodiazepine antagonist. We measured endozepine-2 and endozepine-4 by high-performance liquid chromatography and radioreceptor assay in serum and cerebrospinal fluid from three patients with IRS. During episodes of stupor there was a large (up to 300-fold compared with control patients) increase of endozepine-4 content in cerebrospinal fluid and serum, but a return to normal concentrations between attacks. Endozepine-4 may contribute to, or be the cause of, IRS. The reasons for abnormal concentrations of endozepine in blood and brain are unknown.

Adult↗
PubMed1992

Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene.

BACKGROUND: We previously described two members of a family affected by an apparently genetically determined fatal disease characterized clinically by progressive insomnia, dysautonomia, and motor signs and characterized pathologically by severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Five other family members who died of this disease, which we termed "fatal familial insomnia," had broader neuropathologic changes suggesting that fatal familial insomnia could be a prion disease. METHODS: We used antibodies to prion protein (PrP) to perform dot and Western blot analyses, with and without proteinase K, on brain tissue obtained at autopsy from two patients with fatal familial insomnia, three patients with sporadic Creutzfeldt-Jakob disease, and six control subjects. The coding region of the PrP gene was amplified and sequenced in the samples from the two patients with fatal familial insomnia. Restriction-enzyme analysis was carried out with amplified PrP DNA from 33 members of the kindred. RESULTS: Protease-resistant PrP was found in both patients with fatal familial insomnia, but the size and number of protease-resistant fragments differed from those in Creutzfeldt-Jakob disease. In the family with fatal familial insomnia, all 4 affected members and 11 of the 29 unaffected members had a point mutation in PrP codon 178 that results in the substitution of asparagine for aspartic acid and elimination of the Tth111 I restriction site. Linkage analysis showed a close relation between the point mutation and the disease (maximal lod score, 3.4 when theta was zero). CONCLUSIONS: Fatal familial insomnia is a prion disease with a mutation in codon 178 of the PrP gene, but the disease phenotype seems to differ from that of previously described kindreds with the same point mutation.

Adolescent↗
PubMed1992

Idiopathic recurring stupor: a case with possible involvement of the gamma-aminobutyric acid (GABA)ergic system.

A patient had recurrent spontaneous episodes of stupor or coma in the absence of toxic, metabolic, or structural brain damage. Ictal electroencephalography showed fast 14 Hz background activity; sleep studies excluded narcolepsy. Flumazenil (Anexate), a benzodiazepine antagonist, promptly resolved the episodes and normalized the electroencephalogram. Radioreceptor binding studies showed the presence of a ligand to the central benzodiazepine receptor in plasma and cerebrospinal fluid during the episodes, suggesting a gamma-aminobutyric acid (GABA)ergic system involvement in the origin of the attacks.

Benzodiazepines↗
PubMed1992

Isolated failure of noradrenergic transmission in a case with orthostatic hypotension and hyperactivity of gastro-colic reflex.

We describe a 37-year-old man with a long-standing history of impotence and urgency of defaecation. The latter invariably followed the ingestion of food. Studies of cardiovascular autonomic function disclosed asymptomatic orthostatic hypotension due to isolated sympathetic noradrenergic failure with intact cardiac vagal control. There were no other neurological abnormalities. Levels of plasma noradrenaline and urinary vanillylmandelic acid were very low but plasma dopamine and urinary homovanillic acid were normal. A low level of dopamine-beta-hydroxylase activity was detected in plasma. The patient's parents were first cousins. The parents, the brother and the sister were investigated and clinical and biochemical studies showed no abnormalities. We conclude that this is a further observation of orthostatic hypotension due to isolated adrenergic failure with clinical and biochemical features different from cases previously described.

Adult↗
PubMed1992

Autonomic nervous system function in myotonic dystrophy.

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.

Adolescent↗
PubMed1992

Abnormal sympathetic skin responses in thalamic lesions.

Sympathetic skin responses (SSRs) were abolished in 4 patients affected with fatal familial thalamic degeneration involving the anterior (A) and dorsomedial (DM) thalamic nuclei, without lesions of the peripheral vegetative system. Abnormalities of SSR were not due to peripheral nerve lesions. It is concluded that SSR integrity also depends upon thalamic formations ("visceral" thalamus) and their frontal cortical connections.

Adult↗
PubMed1992

Brain energy metabolism studied by 31P-MR spectroscopy in a case of migraine with prolonged aura.

The brain and skeletal muscle oxidative metabolism of a patient with prolonged aura was studied by phosphorus magnetic resonance spectroscopy. We found that the phosphocreatine to ATP ratio in brain was reduced, while the inorganic phosphate to phosphocreatine ratio and the calculated ADP concentration were increased. The phosphorylation potential and percentage of maximal rate of ATP synthesis were also altered. Intracellular pH and inorganic phosphate concentration were normal. In muscle we found a low post-exercise recovery of phosphocreatine. These data indicate an impairment of energy oxidative metabolism both in brain and muscle.

Adenosine Diphosphate↗
PubMed1992

Fatal familial insomnia: clinical and pathologic study of five new cases.

In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Adult↗
PubMed1992

Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178.

Fatal familial insomnia (FFI), a condition characterized by inability to sleep, dysautonomia, motor disturbances, and selective thalamic atrophy is a prion disease linked to a GAC----AAC mutation at codon 178 of the prion gene. These data were obtained from one kindred. We now report a second kindred affected by FFI and carrying the same mutation. The finding of the same disease phenotype and genotype in a second family further validates FFI as a distinct disease entity and a phenotype of the GAC----AAC mutation at codon 178 of the prion gene.

Base Sequence↗
PubMed1992

Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura.

We studied brain and muscle energy metabolism by phosphorus 31 magnetic resonance spectroscopy (31P-MRS) in 12 patients affected by migraine with aura (classic migraine) in interictal periods. Brain 31P-MRS disclosed a low phosphocreatine content in all patients, accompanied by high adenosine diphosphate concentration, a high percentage of V/Vmax (adenosine triphosphate), and a low phosphorylation potential--features showing an unstable state of metabolism in classic migraine. Abnormal muscle mitochondrial function, in the absence of clinical signs of muscle impairment, was present in nine of the 12 patients examined.

Adenosine Diphosphate↗