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Biomedical subjects

R Manni

Publications and source records attributed to R Manni.

At least 19 recordsLinked to original sources

Sex hormones and pituitary function in male epileptic patients with altered or normal sexuality.

Male epileptic patients frequently complain of sexual dysfunction, particularly impotence and loss of libido. Epilepsy itself, antiepileptic drugs (AEDs), and psychosocial factors are believed to contribute to impaired sexuality. We studied luteinizing hormone (LH) pulsatile secretion, gonadotropin, and prolactin (PRL) responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) in 37 adult male epileptic patients receiving AED monotherapy who were seizure-free and had normal EEGs. Sexuality was assessed by psychological interview. Impotence was diagnosed in 8 patients (in 2 combined with loss of sexual desire). The occurrence of hyposexuality (approximately 20%) was independent of epilepsy syndrome or AED. No change in total testosterone (T) level was observed. Free T (fT) and dihydrotestosterone (DHT) levels were lower and sex hormone binding globulin (SHBG) levels were higher in epileptic subjects than in healthy controls, but a statistically significant difference was not observed between hypo- and normosexual patients. In impotent epileptic patients, estradiol (E2) levels were significantly increased as compared with those of patients with preserved sexuality and of healthy controls. The unbalanced relation between androgen and E2 levels was emphasized by decreased T/E2, fT/E2, and DHT/E2 ratios obtained in hyposexual epileptic patients. In this group, LHRH induced blunted LH peaks. No changes were noted in LH pulsatility features. These findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypogonadotropic hypogonadism.

Adult

Sleep-apnoea and autonomic dysfunction: a cardiopressor and pupillometric study.

Isolated alterations in the autonomic nervous system (ANS) have been described in obstructive sleep-apnea syndrome (OSAS), but the exact nature and degree of ANS involvement in OSAS is as yet uncharted. In the present study we evaluated some autonomic nervous functions in 13 OSAS patients using cardiopressor and pupillometric tests. Almost all showed only slight alterations of ANS function, generally in the form of a hypofunction of both sympathetic and parasympathetic branches. Pupillometry was more sensitive than cardiovascular indexes in detecting neurovegetative involvement which correlated with some respiratory indices. The data suggest that autonomic involvement in OSAS is ascribable to metabolic changes (hypoxia, hypercapnia) rather than to primary "neurogenic" alterations.

Adult

[Encephalitis lethargica].

We report the case of a 34-year old patient who first complained of fever, confusion and transient ophthalmoplegia and then developed akinetic mutism, frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and electrophysiological data support a diagnosis of encephalitis lethargica. Magnetic resonance imaging showed hyperintensive lesions in various brain regions. The patient responded to corticosteroid treatment. Two years after the onset of the first clinical signs he had recovered completely and today, after 5 years, he shows no sign of disease.

Adult

Sex hormones, gonadotropins and prolactin in male epileptic subjects in remission: role of the epileptic syndrome and of antiepileptic drugs.

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of anti-epileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and delta 4-androstenedione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.

Adult

Sleep related breathing patterns in patients with spinal muscular atrophy.

A clinical and polygraphic study of nocturnal sleep was performed in 8 (4 males, 4 females; age range 10-37 years) patients with spinal muscular atrophy, whose baseline respiratory function assessment during wakefulness showed restrictive ventilatory syndrome but blood-gas tension within normal limits. No patient reported any significant sleep complaint suggestive of sleep-disordered breathing. However, in 4 patients HbSaO2 desaturations below 90% (HbSaO2 nadir 68%) were detected during nocturnal polysomnography. The HbSaO2 desaturations occurred during brief central apneas or hypopneas, mainly during REM sleep, the apnoea hypopnea index being within normal limits in all cases. The data suggest that nocturnal polysomnography can detect otherwise clinically silent hypoxemia in SMA patients without any predisposing factor to sleep-disordered breathing other than their illness and still showing normal blood-gas tensions during wakefulness. Further studies are needed to determine the long-term evolution and the prognostic significance of nocturnal hypoxemia in these patients.

Adolescent

A multiparametric investigation of daytime sleepiness and psychomotor functions in epileptic patients treated with phenobarbital and sodium valproate: a comparative controlled study.

Subjective and objective measures of daytime sleepiness and psychomotor function were determined in normal control subjects and in epileptic patients on chronic monotherapy with phenobarbital or valproate (n = 10 in each group). All patients had primary generalized epilepsy with a normal resting EEG and were seizure-free for at least 1 year. After nocturnal polysomnographic recording, each subject was evaluated at 2 h intervals between 10:00 and 16:00 h by using multiple sleep latency tests (MSLT), a visual analogue rating scale for alertness (VARS), an anxiety scale (STAI-X1) and a battery of psychomotor tests. Nocturnal sleep parameters before daytime assessment were comparable in the 3 groups. At MSLT, patients on phenobarbital showed a shorter mean sleep latency (9.0 +/- 1.7 min) compared with the valproate group (12.5 +/- 1.3 min) and controls (12.9 +/- 1.2 min), though within-group variability was considerable. Compared with controls, patients on phenobarbital showed longer motor movement times, impaired attention (cancellation test, CT), reduced processing speed (digit-symbol substitution, DSS) and a trend towards lower critical flicker fusion threshold. Patients on valproate showed some impairment in attention and a trend towards longer motor movement time. In patients, no correlation was found between assessed parameters and serum drug concentrations, which were 19.3 +/- 1.7 micrograms/ml for phenobarbital and 85.7 +/- 4.7 micrograms/ml for valproic acid.

Adult

Drug withdrawal in patients with epilepsy: prognostic value of the EEG.

The role of the inter-ictal EEG in predicting seizure relapse after antiepileptic drug withdrawal (AED-W) is unclear. A prospective study on AED-W is in progress. This trial includes routine and sleep EEG recordings every 3 and 6 months, respectively, at each step of the drug discontinuation and periodically during follow-up. Data obtained for 136 patients (mean age 23.2 years; 63 with Idiopathic Generalized Epilepsy IGE, 73 with Partial Cryptogenic or Symptomatic Epilepsy PE; without associated neuropsychiatric handicap; with at least 1 year of follow-up after AED-W) were analysed. EEG recordings from seizure onset were available for all patients. Data were analysed separately in IGE and PE patients. The presence of inter-ictal epileptiform abnormalities (IEAs) at the seizure onset and just before AED-W does not seem to predict the AED-W outcome. However, results indicate an association between persisting and increased IEAs during AED-W and a higher relapse rate in both groups, which was statistically significant in the IGE patients.

Adolescent

Electrophysiological and immunogenetic findings in recurrent monosymptomatic-type hypersomnia: a study of two unrelated Italian cases.

MSLT and immunogenetic findings in two unrelated Italian subjects with recurrent monosymptomatic hypersomnia are reported. In both patients MSLT documented a markedly increased daytime sleep propensity during the attacks without augmented REM sleep pressure. Both patients share the same HLA haplotype (HLA-DR1, DQ1) which has been found in Kleine-Levin syndrome. This makes these subtypes of recurrent hypersomnia indistinguishable one from the other, under the immunogenetic profile, but permits differentiation from narcolepsy which is HLA-DR2, DQ1 closely linked.

Adolescent

Sleep disorders in neuromuscular diseases.

This article reports the results of several studies on neuromuscular patients (9 Duchenne's muscular dystrophy, 10 myotonic muscular dystrophy, 8 mitochondrial myopathies, 6 spinal muscular atrophy). An evaluation of respiratory function during wakefulness, a sleep questionnaire and an overnight polysomnography were performed in all patients. Recurrent hypoxaemia of variable degree was observed during sleep. In most cases, night-time hypoxaemia appears not to be predictable during wakefulness. Nocturnal hypoxaemia occurs in relation to apnoeas or hypopnoeas, mainly of central type, especially when these breathing irregularities occur during rapid eye movement (REM) sleep. Moreover, polygraphic sleep-apnoea patterns, as defined by international criteria, seem to be an infrequent condition, except for those neuromuscular diseases, characterized by an involvement of the central nervous system.

Adolescent

Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy.

Twenty-five patients with epilepsy (mostly with partial seizures) who had responded favourably to a short-term trial of add-on vigabatrin entered maintenance treatment. After 52 to 78 months, 15 patients continue to take the drug with good therapeutic response. Median monthly seizure frequency during the last 2 months on vigabatrin in all patients, including drop-outs, was 3.5 (range 0-74) as compared with 10 (range 3-98) during an initial placebo period (p < 0.01). Drop-outs were caused by adverse events in 2 cases (ataxia and psychotic symptoms respectively), seizure breakthrough in 4 cases and reasons unrelated to treatment in 4 patients. In most patients, side effects were absent or mild, the most frequent complaint being weight gain. It is concluded that the antiepileptic efficacy and good clinical tolerability of vigabatrin are generally maintained during long-term treatment for up to 6 years.

Adolescent

Nocturnal sleep and oxygen balance in Duchenne muscular dystrophy. A clinical and polygraphic 2-year follow-up study.

A long-term, clinical and polygraphic investigation of nocturnal sleep was performed in nine non-ambulatory Duchenne muscular dystrophy patients (mean age 16.2 years, range 10-20) with normal daytime blood gas tensions. The data show that nocturnal sleep has some adverse influence on oxygen balance in these patients as suggested by the occurrence of arterial oxyhaemoglobin desaturation occurring mainly during REM stages. This adverse effect tended to worsen significantly within a 2-year period in the absence of any sleep-related symptoms. A significant correlation between the degree of oxygen imbalance during sleep and the degree of restrictive thoracic syndrome during wakefulness was shown.

Adolescent

Daytime sleepiness in healthy university students: a multiparametric study.

A multiparametric investigation of daytime sleepiness was performed in 18 healthy young university students. After undergoing a standard polysomnographic recording at home the night before, all subjects were evaluated by Multiple sleep latency test (MSLT) at 10.00, 12.00, 14.00, 16.00, 18.00. Subjective sleepiness (by using Visual Analogue Rating Scale) and performance tasks (Cancellation Test, Digit Symbol Substitution, Choice Reaction Time, Critical Flicker Fusion Threshold) were also assessed at the same times. Mean daily sleep latency was found to be about 10 minutes, with several individual values in the borderline range (greater than 5 less than 10 minutes). Subjects did not rate themselves as excessively sleepy and there was no correlation between subjective and objective estimates of sleepiness. No consistent correlation was found between subjective-objective sleepiness and results of performance tests. Anxiety trait (Spielberg State Anxiety Trait) did not correlate with sleepiness, but higher anxiety scores were significantly associated with poor performance. These results confirm the occurrence of fairly marked objective drowsiness in healthy young subjects which, however, was not associated with subjective sleepiness and did not adversely affect performance on a variety of tests of CNS function.

Adult

Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients.

1. The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2. Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P less than 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P less than 0.05) in patients taking sodium valproate. 3. Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 +/- 2.0 h vs 9.1 +/- 3.4 h, means +/- s.d., P less than 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 +/- 1.8 h) were similar to those found in controls.

Adult

Hypersomnia in dystrophia myotonica: a neurophysiological and immunogenetic study.

Ten patients with dystrophia myotonica (8 adults and 2 prepubertal children), from three unrelated families, were investigated for diurnal sleepiness, using a sleep questionnaire and multiple sleep latency test (MSLT). Immunogenetic study was also carried out to assess the involvement of HLA region genes in modulating susceptibility to excessive diurnal sleepiness (EDS). EDS was reported by 5 patients and confirmed in each case by MSLT. In the whole patients group, mean daytime sleep latency was significantly shorter than in healthy controls matched for age and sex. At clinical or neurophysiological evaluation, EDS did not show the features associated with the narcoleptic type. In only one case hypersomnolence could be explained by underlying sleep-disordered breathing. HLA patterns were different from those frequently observed in the narcoleptic or non-narcoleptic types of hypersomnia. In patients with EDS, the frequency of the DQW1 and particularly of the DRW6-DQW1 haplotype appeared to be over-represented.

Adult

Respiratory patterns during sleep in mitochondrial myopathies with ophthalmoplegia.

Nocturnal polygraphic recordings (electroencephalography, electro-oculography, submental and intercostal muscle electromyography, electrocardiography, respiration by thoracic strain gauges and oronasal thermistors) with continuous monitoring of arterial oxyhemoglobin saturation by pulse oximeter were performed in 8 patients with ophthalmoplegia plus. All patients except 1 had normal blood gas values and normal lung volumes associated with a diminished ventilatory response to inhaled CO2 during wakefulness. Four patients showed pathological sleep-related breathing patterns consisting of sleep apneic polygraphic tracings mainly of the central type or of REM-related hypoventilation episodes. It is suggested that these disorders in patients with ophthalmoplegia plus may have a central origin and be related to the underlying metabolic disturbance.

Adult

Effect of different fractions of alkaline reflux on the gastric stump and the esophagus: an experimental research on pigs.

An experimental study was conducted to evaluate the effect of different fractions (bile and pancreaticoduodenal secretions) on the gastric stump and esophageal mucosa. Twenty pigs underwent partial gastrectomy (two-third distal) and cardiomyotomy in order to induce free gastroesophageal reflux. Then, reconstruction of the alimentary tract was performed to assess the effects of different types of alkaline reflux. A combined (biliary and pancreaticoduodenal) reflux, an isolated biliary reflux, and an isolated pancreaticoduodenal reflux were induced, respectively, in three different groups of five pigs each. In a control group a Roux-en-Y gastrojejunostomy was performed. Nine months later, the animals were sacrificed, the esophagus and the gastric stump were removed for histologic examination. The results show that the most severe histopathological lesions are determined by combined alkaline reflux; on the other hand, separated fractions can induce only mild changes on the gastric stump and esophageal mucosa.

Alkalies

Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy.

A night-time polygraphic sleep recording with continuous HbSaO2 monitoring was performed in 11 chair-bound Duchenne muscular dystrophy patients with severe restrictive lung disease but with blood gas values within normal limits when awake. No abnormalities of sleep pattern were detected. Nocturnal sleep did not have significant adverse effects on respiration. However, in 6 patients, infrequent central apnoeas or hypopnoeas occurred which were associated with falls in HbSaO2 greater than those that have been reported to be in normal subjects. The magnitude of HbSaO2 falls appeared to be significantly correlated with functional residual capacity values. Overall, the findings revealed a relatively preserved, although unstable, blood O2 balance during nocturnal NREM and REM sleep in patients with Duchenne muscular dystrophy, even in an advanced stage of their illness.

Adolescent

Time-dependent pharmacodynamic effects of phenobarbital in humans.

The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design. Compared with the placebo session, phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF), whereas no significant effects were detected on choice reaction times, tappings, and digit symbol substitutions. There was a clear-cut dissociation between the time course of serum phenobarbital levels, which remained at a plateau throughout most of the period of observation (up to 72 h) and its subjective (VARS) and objective (CFF) effects, which could be documented only for up to 9 h after administration. These data suggest that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. Multiple Sleep Latency Tests (MSLTs) were also performed in the same subjects and showed that phenobarbital increases diurnal drowsiness and attenuates the circadian variation in drowsy state that is seen under control conditions. MLSTs appeared to be superior to other tests in documenting the sedative effects of the barbiturate.

Adult