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Biomedical subjects

M Leone

Publications and source records attributed to M Leone.

At least 109 records · Page 6Linked to original sources

Genetic abnormalities of the protein C system: shared risk factors in young adults with migraine with aura and with ischemic stroke?

Migraine, particularly migraine with aura (MA), may be a risk factor for ischemic stroke (IS). The reasons for this association are unknown. We investigated the presence of genetic abnormalities of the protein C system in 83 MA patients, 31 IS patients, and 124 healthy controls, all aged under 45 years. We found an increased frequency of activated protein C resistance due to Arg506Gln factor V mutation, and of protein S deficiency in both disorders, with figures higher than those reported in the general population and significantly different from those found in controls. These prothrombotic genetic abnormalities may be shared risk factors in IS and MA, and may play a role in increasing the risk of cerebrovascular disease in migraineurs.

Activated Protein C Resistance↗

Abnormal 24-hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache.

The typical cyclic occurrence of cluster headache suggests the involvement of hypothalamic rhythm regulating centers in the pathogenesis of this primary headache. In previous studies, reduced 24-h plasma melatonin levels during the cluster period, loss of circadian melatonin secretion in remission, as well as permanently reduced excretion of urinary melatonin in both illness phases have been reported, supporting the hypothesis of a hypothalamic derangement. In this study, the 24-h urinary excretion of the main melatonin metabolite, 6-sulphatoxymelatonin, was evaluated in 20 cluster period cluster headache patients. Thirteen were retested 12 months later, in the same period of the year, during remission. Fourteen age- and sex-matched healthy subjects were the controls. As expected, significantly higher levels of 6-sulphatoxymelatonin were present in nocturnal urine than in day-time urine in controls, while in both cluster headache groups urinary levels of this metabolite did not differ between day and night. Nocturnal levels of 6-sulphatoxymelatonin were significantly lower in both cluster headache groups than controls. Day-time levels did not differ significantly between the groups. Altered excretion of urinary 6-sulphatoxymelatonin even during remission indicates that at least some of these anomalies are independent of the pain, and provides further evidence of involvement of the hypothalamic rhythm regulating centers in cluster headache.

Adult↗

Biofeedback-assisted relaxation training for young adolescents with tension-type headache: a controlled study.

Tension-type headache is common in children and adolescents and is generally treated with medication, but emerging literature suggests that various behavioral treatments may provide efficacious alternatives to medication. Juvenile tension-type headache sufferers were randomly assigned to biofeedback-assisted relaxation continued to improve and were superior to the control condition at a 6- and 12-month follow-up (86% versus 50%). Biofeedback-assisted relaxation appears to be an efficacious and durable treatment for juvenile tension-type headache and merits further exploration.

Adolescent↗

Modification of alpha-chain or beta-chain heme pocket polarity by Val(E11) --> thr substitution has different effects on the steric, dynamic, and functional properties of human recombinant hemoglobin. Deoxy derivatives.

The dynamic and functional properties of mutant deoxyhemoglobins in which either the beta-globin Val67(E11) or the alpha-globin Val62(E11) is replaced by threonine have been investigated through the thermal evolution of the Soret absorption band in the temperature range 300 to 20 K and through the kinetics of CO rebinding after flash photolysis at room temperature. The conformational properties of the modified alpha chain and beta chain distal heme pockets were also studied through x-ray crystallography and molecular modeling. The data obtained with the various techniques consistently indicate that the polar isosteric mutation in the distal side of the alpha chain heme pocket has a larger effect on the investigated properties than the analogous mutation on the beta chain. We attribute the observed differences to the presence of a water molecule in the distal heme pocket of the modified alpha chains, interacting with the hydroxyl of the threonine side chain. This is indicated by molecular modeling which showed that the water molecule present in the alpha chain distal heme pocket can bridge by H bonding between Thr62(E11) and His58(E7) without introducing any unfavorable steric interactions. Consistent with the dynamic and functional data, the presence of a water molecule in the distal heme pocket of the modified beta chains is not observed by x-ray crystallography.

Carbon Monoxide↗

A case-control study on alcohol and seizures: study design, protocol, and data collection. The ALCE (Alcohol and Epilepsy) Study Group.

We designed a multicenter case control study to evaluate whether chronic alcoholism and alcohol are risk factors for developing a first generalized tonic-clonic epileptic seizure. Cases were 278 patients (92 women, 186 men), with a first generalized tonic-clonic seizure (either idiopathic or symptomatic), matched to 556 controls for center, sex, age, and weekday of the seizure. Information on risk factors was obtained through a questionnaire. This paper focuses on the study design (selection of cases and choice of controls), the validity of the instruments for data collection, and the strategies of study conduction (interviews, use of proxy respondents). Inter-rater agreement was excellent for drinking status, patterns of drinking, and broad indicators of consumption (yes/no). Agreement was variable for the number of servings/week, but was excellent (r = 0.91) for a summary of daily alcohol intake.

Adult↗

Hepatitis C virus infection among institutionalised psychiatric patients: a regression analysis of indicators of risk.

BACKGROUND/AIMS: Institutionalised psychiatric patients are at increased risk of developing chronic infection with hepatitis B virus (HBV). However, little information is available on transmission and epidemiology of hepatitis C virus (HCV) in this setting. The aim of this study was to identify potential risk factors of acquiring HCV infection in two large psychiatric institutions in northern Italy. METHODS: We designed a case-control study using randomly selected controls from the same study database, consisting of a total of 1180 patients, in order to satisfy the principle that both cases and controls should be representative of the same base experience. A multiple regression logistic analysis was used to identify features that could predict exposure to HCV as evidenced by the presence of circulating anti-HCV antibodies. RESULTS: Anti-HCV was detected in 79 patients (6.7%). The prevalence of viraemia and the distribution of genotypes were very similar to those found in subjects with chronic HCV infection drawn from the same geographical area. Multivariate analysis indicated that a diagnosis of psychosis and a history of trauma were statistically significant independent risk factors associated with a positive anti-HCV result (OR 2.615, 1.273-5.373 95% CI and OR 2.096, 1.133-3.877 95% CI, respectively). CONCLUSIONS: The findings of this large epidemiological study show for the first time that prolonged residence in psychiatric institutions does not entail per se a significant risk of acquiring HCV infection. Since transmission of HCV in this setting appears to occur predominantly via classical parenteral routes, simple prophylactic measures appear to be adequate to prevent infection.

Adult↗

The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity.

The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at -30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima (delta maximum = maximum response - baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol (p < 0.02) and increased PRL (p < 0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels (p < 0.05) and reduced basal PRL plasma levels (p = 0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.

Case-Control Studies↗

Coexistence of migraine and cluster headache: report of 10 cases and possible pathogenetic implications.

We report on 10 patients suffering from two types of primary headache, migraine and cluster, diagnosed according to IHS criteria, and selected from headache patients attending two Italian headache centers. We briefly review the literature on coexisting migraine and cluster headache, considering the time relationships between these two headaches. The present series seems not to confirm the hypothesis that migraine transforms into cluster headache since both headaches persist together in the patients. The series is of clinical interest particularly with regard to diagnosis and to treatment strategies. Furthermore, while migraine and cluster headache comorbidity must be confirmed by population-based epidemiological studies, the possibility arises that the two conditions may be linked pathophysiologically: common genetic factors or functional alterations in the same central neurological circuits may play a role in the pathogenesis of both disorders.

Adult↗

Transdermal clonidine in the prophylaxis of episodic cluster headache: an open study.

Transdermal clonidine has recently been reported to be efficacious in the prophylaxis of cluster headache. A 2-week course of transdermal clonidine (5 mg the first week, 7.5 mg the second week) preceded by a 5-day run-in period, was administered to 16 patients with episodic cluster headache in an active cluster period. In 5 patients, the painful attacks disappeared after the seventh day of treatment. For the group as a whole, no significant variations in headache frequency, pain intensity, or attack duration were observed between the run-in period and the first and second weeks of treatment (ANOVA). Further studies are necessary to clarify the effectiveness of transdermal clonidine in the prophylaxis of episodic cluster headache.

Administration, Cutaneous↗

Alcohol use is a risk factor for a first generalized tonic-clonic seizure. The ALC.E. (Alcohol and Epilepsy) Study Group.

We performed a multicenter case-control study to estimate whether chronic alcoholism and alcohol consumption are risk factors for developing a first generalized tonic-clonic seizure (GTCS). We studied 237 first-seizure patients (158 men, 79 women) matched to 474 hospital controls for center, sex, age (+/-5 years), and weekday of the seizure. The risk of first GTCS in alcoholics was greater than in non-alcoholics for men (odds ratio, 6.8; 95% confidence limits, 3.6-13.0) and women (6.8, 1.6-32.6). The odds ratio (both sexes) was 1.2 (0.8-1.8) for an average daily intake of absolute alcohol of 1 to 25 g/day and rose with the amount of alcohol consumed daily: 1.3 (0.8-2.1) for 26 to 50 g/day, 3.0 (1.7-5.4) for 51 to 100 g/day, 7.9 (2.9-21.9) for 101 to 200 g/day, and 16.6 (1.9-373.4) for >200 g/day. Our study provides evidence of a powerful association between alcohol use, alcoholism, and the first GTCS.

Alcohol Drinking↗

[Computerization experience in a day hospital of integrated radiochemotherapy].

INTRODUCTION: We report on a cost-effective easy-access software developed for the functional integration of the clinical records and history of oncologic patients with the management of the Day Hospital of the Radiotherapy Department of the University Hospital A. Gemelli, in Rome. MATERIAL AND METHODS: The software was designed to archive the clinical records and history of oncologic patients and the relative chemotherapy, to manage the examination scheduling, to draw up nursing files with the planned therapy and to make statistical analyses of the department activity. Five forms are available: the patient form, recording patient data; the admission form, recording the type of therapy (e.g., chemotherapy, tests, medical examinations, etc.), the relative cost and chemotherapy protocol, detailing for instance the type of drug; the nursing file, detailing chemotherapy schedule and the dilution of each drug; the menu, to select and retrieve any record. The minimum configuration requires a 386 Intel CPU, 4 Mb RAM and 4 Mb free on the hard disk. The software is the File Maker Pro 2.1 for Windows which can interact with Apple Macintosh computers. RESULTS: Since October, 1995, we have saved the clinical records of 272 oncologic outpatients (2415 entries in all), with a mean of 201/month. This computer system permitted us to save and retrieve data for both clinical and didactic purposes and to plan our activity. CONCLUSIONS: One year after it was implemented and used in clinical practice, the system is a cost-effective and user-friendly tool for the management of the Radiochemotherapy Day Hospital of our Radiotherapy Department.

Combined Modality Therapy↗

Low temperature optical spectroscopy of low-spin ferric hemeproteins.

We report the Soret absorption spectra (500-350 nm) of the cyanomet derivatives of human hemoglobin and horse myoglobin, in the temperature range 300-20 K and in two different solvents (65% v/v glycerol-water or 65% v/v ethylene glycol-water). In order to obtain information on stereodynamic properties of active site of the two hemeproteins, we perform an analysis of the band profiles within the framework of electron-vibrations coupling. This approach enables us to single out the various contributions to the spectral bandwidth, such as those arising from non-radiative decay of the excited electronic state (homogeneous broadening) and from the coupling of the electronic transition i) with high frequency modes (that determines the vibronic structure of the band) and ii) with a "bath" of low frequency modes (that is responsible for the temperature dependence of the experimental spectra). We discuss the relevant parameters and their temperature dependence and compare them with the ones already reported for other derivatives of the same hemeproteins in the same solvents. In particular, non-harmonic contributions to soft modes are found, for cyanomet derivatives, to be larger than those observed for liganded carbonmonoxy but smaller than those observed for unliganded deoxy derivatives. The reported data enable us to obtain information on the dependence of stereodynamic properties of the heme pocket upon iron oxidation state, dimensions of the exogenous ligand and composition of the external matrix.

Animals↗

Structural fluctuations of myoglobin from normal-modes, Mössbauer, Raman, and absorption spectroscopy.

A normal-mode analysis of carbon monoxymyoglobin (MbCO) and deoxymyoglobin (Mb) with 170 water molecules is performed for (54)Fe and (57)Fe. A projection is defined that extracts iron out-of-plane vibrational modes and is used to calculate spectra that can be compared with those from resonance Raman scattering. The calculated spectra and the isotopic shift (57)Fe versus (54)Fe agree with the experimental data. At low temperatures the average mean square fluctuations (MSFs) of the protein backbone atoms agree with molecular dynamics simulation. Below 180 K the MSFs of the heme iron agree with the data from Mossbauer spectroscopy. The MSFs of the iron atom relative to the heme are an order of magnitude smaller than the total MSFs of the iron atom. They agree with the data from optical absorption spectroscopy. Thus the MSFs of the iron atom as measured by Mossbauer spectroscopy can be used to probe the overall motion of the heme within the protein matrix, whereas the Gaussian thermal line broadening of the Soret band and the resonance Raman bands can be used to detect local intramolecular iron-porphyrin motions.

Heme↗

Near-infrared spectra of Scapharca homodimeric hemoglobin: characterization of the deoxy and photodissociated derivatives.

The near-infrared charge transfer band at 760 nm (band III) has been investigated in deoxy and photodissociated dimeric Scapharca hemoglobin. At 300 K, the 10-ns spectrum of the carbonmonoxy derivative photoproduct is shifted by about 6 nm toward longer wavelengths with respect to the deoxy spectrum, both in buffer and in glycerol/buffer solutions. Moreover, the band III peak occurs at about the same wavelength at 300 K and at 10 K for the 10-ns photodissociated derivative, whereas in the deoxy derivative large changes in peak position and linewidth are observed as a function of temperature. These findings suggest that in dimeric Scapharca hemoglobin the photoproduct has not relaxed after 10 ns. The complete time dependence of the relaxation process has been studied both in buffer and in glycerol/buffer solutions at room temperature. The relaxation from the photoproduct to the deoxy species occurs on a microsecond time scale, in line with recent optical absorption and resonance Raman measurements.

Animals↗

Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups.

A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n = 10) or placebo (n = 10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p < 0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p < 0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.

Adult↗

Familial cluster headache: report of three families.

We report on three families in which cluster headache is present in more than one member. In one of these families a boy, his father, and paternal grandfather were affected. In the other two families, a father and son and mother and daughter were the affected members. Diagnoses were based on IHS criteria, after examining and taking the history directly from the patient in all but one of the seven cases; the seventh patient was deceased and the diagnosis was based on reports from the affected son. Considered in the light of other recent reports of familial cluster headache, these cases suggest that cluster headache can have a genetic component.

Adult↗