Biomedical subjects

P Avoni

Publications and source records attributed to P Avoni.

30 records · Page 2Linked to original sources

PubMed1995

Dissociated 24-hour patterns of somatotropin and prolactin in fatal familial insomnia.

To assess the changes in the 24-hour profiles of serum somatotropin and prolactin levels during total disruption of the sleep/wake cycle sustained over several months, we studied 2 subjects affected by fatal familial insomnia, a rare disease characterized by selective thalamic degeneration that causes chronic sleep loss. Under standardized conditions and polysomnographic control, the patients underwent repeated 24-hour study sessions covering the entire clinical course of the disease. Hormones were assayed at 30-min intervals. Four healthy volunteers were used as controls. A sleep/wake cycle was always absent in fatal familial insomnia. Serum somatotropin and prolactin concentrations never exceeded the normal range of variation. The nocturnal elevation of somatotropin disappeared simultaneously with sleep loss, whereas a significant 24-hour component of variations in serum prolactin levels was present for months after total disruption of the sleep/wake cycle, with normally placed nocturnal acrophases. Complete obliteration of the 24-hour component was achieved for prolactin only in the advanced stages, through a progressive decrease in 24-hour amplitude of variation. Selective and progressive degeneration of the mediodorsal and anterior ventral nuclei of the thalamus causes an early obliteration of the 24-hour rhythm of somatotropin and a later disappearance of circadian prolactin rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Tardive pain.

Explore the source record for details and available documents.

Aged↗

PubMed1994

Diurnal blood pressure variation and hormonal correlates in fatal familial insomnia.

Fatal familial insomnia is a prion disease in which a selective thalamic degeneration leads to total sleep deprivation, hypertension, dysautonomia, adrenal overactivity, and impaired motor functions. With patients under continuous recumbency and polysomnographic control, we assessed the changes in the 24-hour patterns of blood pressure, heart rate, plasma catecholamines, corticotropin, and serum cortisol in three patients at different stages of the disease. Six healthy volunteers were used as control subjects. A dominant 24-hour component was detected at rhythm analysis of all variables, both in patients and control subjects. In the patients, the amplitudes gradually decreased as the disease progressed, leading to the obliteration of any significant dirunal variation only in the preterminal stage. A shift in phase corresponded to the loss of the nocturnal fall in blood pressure in an early stage of the disease, when nocturnal bradycardia was still preserved. Plasma cortisol was high and became increasingly elevated, whereas corticotropin remained within normal levels; abnormal nocturnal peaks appeared in their circadian patterns. The disrupted patterns of cortisol and blood pressure preceded the development of hypertension and severe dysautonomia, which in turn were paralleled by increasing catecholamine and heart rate levels. Our data demonstrate that in patients with fatal familial insomnia the changes detectable in the rhythmic component of diurnal blood pressure variability result in a pattern of secondary hypertension. Disturbances in thalamic, pituitary-adrenal, and autonomic functions seem to be involved in mediating these changes.

Adrenocorticotropic Hormone↗

PubMed1994

Progressive disruption of the circadian rhythm of melatonin in fatal familial insomnia.

Fatal familial insomnia (FFI) is a disease characterized by loss of sleep activity due to selective thalamic degeneration. To assess the secretory pattern of melatonin (MT) in FFI, we studied two cases of overt disease under standardized conditions and polysomnographic control. Each patient underwent repeated 24-h study sessions, and MT was assayed at 30-min intervals. Six healthy volunteers were used as controls. Slow wave sleep was never recorded, whereas occasional episodes of enacted dreaming accompanied by rapid ocular movements and complex muscular activities were documented, with no detectable rhythm. Plasma MT concentrations gradually decreased as the disease progressed. A significant circadian rhythm was detected in the earlier recordings, with decreasing amplitudes with disease progression. Complete rhythm obliteration was achieved in the most advanced stage. Normally placed nocturnal acrophases were detected in the earlier stages, but then a shift toward the daytime hours was observed. Thalamic lesions of FFI appear to determine a progressive disruption of the sleep/wake cycle accompanied by decreased circulating levels of MT, with progressive alterations in the circadian rhythm of this hormone. On the other hand, decreased secretion of MT may contribute to the sleep disturbances of FFI.

Adult↗

PubMed1994

Idiopathic recurring stupor.

Idiopathic recurring stupor (IRS) is a disease of unknown pathogenesis presenting with recurrent stuporous states. We describe three IRS patients in whom there were no metabolic, toxic, or structural brain dysfunctions. Ictal EEGs were characterized by fast (14- to 16-Hz), unreactive background activity. Flumazenil, a benzodiazepine receptor antagonist, promptly resolved the clinical and EEG picture. In all patients, ictal plasma determination showed a marked increase in benzodiazepine-like activity identified as endozepine-4. IRS may be due to an unexplained excess of endozepine-4.

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

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

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↗

PubMed1991

Cardiovascular dysautonomia in fatal familial insomnia.

Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia. The diagnosis was confirmed at autopsy in patient 1. In the resting state blood pressure and heart rate were higher than controls in patient 1; plasma noradrenaline levels were elevated in both patients. Evaluation of cardiovascular reflexes indicated intact baroreflex pathways but with exaggerated blood pressure and biochemical responses to certain stimuli (postural change, Valsalva manoeuvre, isometric handgrip). There was no pressor response to intravenously infused noradrenaline, an increased response to atropine and diminished depressor and sedative effects to clonidine. Overall these results are indicative of an unbalanced autonomic control with preserved parasympathetic and higher background and stimulated sympathetic activity. These physiological, biochemical and pharmacological data, together with known neuro-pathological findings in this disorder, emphasize the possible role played by the thalamus in regulating autonomic control of cardiovascular function in man.

Adult↗

PubMed1991

Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family.

Three siblings of a family affected with Leber's hereditary optic neuropathy (LHON) showed a mitochondrial DNA mutation at position 11778. The lactate response to a standardized effort was increased in only one case. Muscle biopsies and biochemistry of muscle and platelet mitochondrial enzymes were normal. All patients showed an altered energy metabolism during exercise and during recovery after exercise on phosphorus 31-magnetic resonance spectroscopy (31P-MRS) of muscle. Brain 31P-MRS showed a decreased energy reserve (decreased PCr/Pi ratio) in all patients. 31P-MRS noninvasively demonstrated an altered mitochondrial energy metabolism in muscle and, for the first time, in the brains of LHON patients.

Adenosine Triphosphate↗

PubMed1991

Circadian hormonal rhythms in two new cases of fatal familial insomnia.

We used a chronobiological inferential statistical method to investigate circadian rhythms of hypophyseal hormones, cortisol, melatonin and catecholamines in two females of the same family affected by fatal familial insomnia. Case 1 (confirmed at autopsy) presented an absent or progressive loss of circadian rhythms of all hormones. In case 2 there was a loss of GH circadian rhythm and a less significant rhythm for melatonin, catecholamines and gonadotropins. These results confirm the role of the thalamus in regulating hormonal circadian rhythm.

Adult↗

PubMed1990

Response to a standard oral levodopa test in parkinsonian patients with and without motor fluctuations.

The acute dose-response profile of a standard oral levodopa dose was followed, over a maximum 8-h period, in 13 patients with and 10 patients without motor fluctuations using a battery of motor quantitative tests (tapping and walking speed, and multiple choice reaction and movement times). Thirteen age-matched normal controls performed tapping and psychomotor tests, at the same time intervals, over a 4-h period. Tapping test and movement times proved significantly impaired in all patients and were the best indicator of levodopa effect, while walking speed and reaction times were apparently of less value, except in severely affected patients. The duration of the levodopa antiparkinsonian effect differed markedly between the two groups, since fluctuating patients returned to prelevodopa dose values within 4 h (mean +/- SEM: 203 +/- 16 min), while in the stable group motor scores remained significantly higher than baseline values up to at least 7 h postdose. The magnitude of the effect was similar in the two groups, but response was complicated by mild to severe dyskinesias in 9 of 13 fluctuating subjects. The pharmacokinetic parameters of levodopa were almost identical in the two groups. Our data add further weight to the hypothesis that cerebral pharmacokinetic or pharmacodynamic factors are responsible for motor fluctuations. Oral levodopa doses coupled with objective tests of motor performance may prove a practical clinical tool to assess and optimize the relationship between drug dose and therapeutic effect.

Adult↗