A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

Low total cholesterol predicts mortality in the nondemented oldest old.

Several studies have demonstrated the importance of hypercholesterolemia as a cardiovascular risk factor and a direct correlation between the reduction in cholesterolemia and the reduction in cardiovascular mortality in populations younger than 65 years. This correlation is controversial in the elderly and, particularly, in the oldest old. The aim of our study was to evaluate the total cholesterol in the oldest old and to assess the eventual presence of correlation between total cholesterol levels and mortality in a group of nondemented oldest old. A subsample of 40 subjects was extracted from the 103 subjects aged over 84 years living in Troina, a rural village in Sicily. We excluded all subjects under therapy with lipid-lowering drugs, demented, with malnutrition or affected by acute or chronic diseases which might cause death in the short term. At the end, 23 subjects (15 males and 8 females) were included in the study. After 2 years, mortality data of all subjects included in the study were obtained from official registers. The statistical analysis was performed by means of the X(2) test. In all subjects the mean of total cholesterol was of 182+/-32 mg/dl (mean+/-SD) and the body mass index was above 20; 17 subjects were in the normal range, 3 were moderately over-weighed and 3 were severely over-weighed. Overall, mortality rate after 2 years was 30% (7 subjects, 4 males and 3 females). We evaluated the relationship between mortality and 4 factors: sex, age, body mass index (BMI) and serum total cholesterol. Mortality was significantly correlated (p<0.002) only with a low level of total serum cholesterol

Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.

OBJECTIVE: Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD). DESIGN: The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. METHODS: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h. RESULTS: Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). CONCLUSIONS: The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.

Circulating endothelin-1 levels in patients with "a frigore" vascular acrosyndromes.

The present study was designed to examine the role of endothelin-1 (ET-1), an endothelium-derived potent long-acting vasoconstrictor peptide, in vascular acrosyndromes with hypersensitivity to cold. Plasma ET-1 concentration was measured, before and after cold test, in 12 subjects with "a frigore" vascular acrosyndromes (9 females and 3 males, age range 17-59 years), of whom 6 were with primary Raynaud's phenomenon and 6 with essential acrocyanosis, and in 6 controls (5 females and 1 male, age range 21-37 years). Cold stimulation was performed by immersion of one hand into a water bath at 13 degrees C for 5 minutes. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral arm at baseline, at the stop of cooling, at 10 and 90 minutes from the beginning of the cold challenge. Mean (+/-SD) baseline ET-1 plasma levels, as measured by radioimmunoassay, were higher in patients with "a frigore" vascular acrosyndromes (4.8 +/- 0.3 pmol/l) than in control subjects (1.9 +/- 0.1 pmol/l, p < 0.001). After hand cooling ET-1 rose in patients with "a frigore" vascular disorders to a peak value of 7.0 +/- 0.4 pmol/l, which was much greater than that observed in healthy subjects (2.7 +/- 0.4 pmol/l, p < 0.001). Absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with "a frigore" vascular acrosyndromes than in normal subjects (2.2 +/- 0.3 vs 0.8 +/- 0.2 pmol/l, p < 0.001), being only in the former group the rise in ET-1 still detected 90 minutes after cold test. Plasma levels of ET-1 in the controlateral arm raised in a similar fashion, but absolute values were lower than in cooled arm. Circulating ET-1 levels in patients with primary Raynaud's phenomenon and essential acrocyanosis showed a similar pattern during the study. Our data demonstrate that in patients with "a frigore" vascular acrosyndromes baseline and cold-stimulated plasma ET-1 concentrations are increased. Further, in these vascular disorders, exaggerated ET-1 response to cold is prolonged. These findings suggest that increased ET-1 may contribute to an imbalance between vasoactive mediators in the cutaneous blood vessels contributing to the abnormal vasoconstriction to cold in these disorders. Alternatively, the increment in ET-1 release may represent a marker for endothelial cell damage in "a frigore" vascular acrosyndromes.

Somatosensory evoked potentials in patients affected by unilateral cerebrovascular lesions with onset during the perinatal period or adulthood.

Unilateral cerebrovascular lesions occurring during adulthood have been reported to be accompanied by high-amplitude somatosensory evoked potentials over the nonaffected hemisphere; however, the mechanisms by which somatosensory evoked potential amplitude increases over the nonaffected hemisphere are still unclear. To investigate the eventual presence of similar amplitude abnormalities in children, we recorded somatosensory evoked potentials in three groups of patients: one with unilateral cerebrovascular lesions that occurred during the perinatal period and another two with unilateral cerebrovascular lesions occurring during late adulthood or old age. Group 1 was comprised of 12 children and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered from unilateral cerebrovascular lesion with perinatal onset. Four control groups were arranged with age matched to that of the patients. Adult patients were subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12 males and 6 females) on the basis of the presence or absence of sensory impairment over the hemiplegic side. In group 1, the four youngest subjects, aged less than 6 years, were found to show somatosensory evoked potentials of abnormally high amplitude over the nonaffected hemisphere, with a "giant" main negative wave at around 45 ms (range 38.7-49.2), strictly localized over the central areas contralateral to the lesion; in normal controls, there was no such wave. All patients in group 2 were found to be affected by large infarctions in the territory of the middle cerebral artery, whereas patients in group 3 presented with subcortical lesions of the internal capsule isolated or in association with an involvement of the frontal and/or temporal cortex. Regarding somatosensory evoked potential parameters measured over the nonaffected hemisphere in adult/elderly subjects, a significant difference was observed for N20 and P22 latency, which was longer in both groups of patients than in controls. There is a significant difference in the neurophysiologic consequences of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere, if it occurs during early infancy or during adulthood. Our findings show a new type of "giant" somatosensory evoked potentials in some children affected by unilateral cerebrovascular lesion with perinatal onset.

Home pharmacological therapy in an ultra-75 years old population in Troina (inner Sicily).

In a group of 365 subjects, 75 years old and ultra, living in Troina (Sicily), a study on prevalence of dementia has been carried out. In the questionnaire, used to collect information about subjects' health, one of the questions concerned the assumption of drugs. The interviewer transcribed the name of the drugs and then coded the related chemical-pharmacological classification, according to the 14 principal groups of the guide of the National Health Service. Up to 9 drugs, on a daily basis, were registered. The total amount of prescriptions was 889, equal to 2.4 per person, with a clear prevalence of the females. 26.1% of the sample did not take any drug. The mode of assumptions was 3 a day. The cardiovascular system is at the top of prescriptions, with 39% of the total, followed by the gastroenteric apparatus and metabolism (17.9%), the nervous system (16.7%), the haemopoietic system (8.4%), the musculo-skeletal system (6.2%), the respiratory apparatus (5.7%), and so on the others. For each principal group of drugs, those more represented are identified, obtaining other information about the practitioners' choices. Among the principal subgroups of cardiovascular system, it is worth mentioning anti-hypertensives, diuretics and antianginal, each of them with their own subgroups. In the gastroenteric apparatus and metabolism group, the latter comprises the drugs for the treatment of diabetes: oral hypoglicaemics and insulin. These drugs allow to identify 34 cases of diabetes: 29 NIDD and 5 IDD. Analogous evaluations for drugs of other groups and comparisons with a few data available in literature are carried out. Surveying the drugs used in a population is useful: (i) to evaluate the health state; (ii) to identify the dominant disease; (iii) to draw comparisons with other populations; (iiii) to follow the evolution of pharmacotherapy.

Plasma endothelin-1 concentrations in non-insulin-dependent diabetes mellitus and nondiabetic patients with chronic arterial obstructive disease of the lower limbs.

BACKGROUND: Endothelin-1 (ET-1), a vasoconstrictor and mitogenic endothelium-derived peptide, has been considered as a marker for endothelial damage and potential contributor to the development of the atherogenic process. METHODS: To evaluate the pattern of plasma ET-1 secretion in non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic patients with chronic arterial obstructive disease (CAOD) of the lower limbs, plasma levels of ET-1 were determined in 12 NIDDM patients (10 men and 2 women; mean age 63+/-8 years) with CAOD of the lower limbs at Fontaine stage II and in 12 nondiabetic patients (11 men and 1 woman; mean age 62+/-4 years) with comparable arteriopathy. Ten normal subjects comprised the control population. RESULTS: The plasma levels of ET-1 in NIDDM patients with CAOD of the lower limbs were 5.7+/-0.3 pmol/L, which represented a significant (p<0.001) difference from the values in nondiabetic patients with comparable arteriopathy (4.1+/-0.6 pmol/L) and those in the control group (2.7+/-0.7 pmol/L). Plasma levels of ET-1 showed a significant (p<0.0001) positive correlation with the levels of fasting insulin in NIDDM patients with CAOD of the lower limbs. Increased plasma ET-1 could reflect a major and/or more diffuse endothelial cell damage or dysfunction in NIDDM than in nondiabetic patients with comparable CAOD of the lower limbs. Augmented mitogenic ET-1 levels could also have a role both in diabetic and nondiabetic angiopathy. CONCLUSIONS: The positive correlation between ET-1 plasma levels and fasting insulin levels in NIDDM patients with CAOD of the lower limbs suggests that the increased ET-1 release could be related to the augmented insulin secretion in these patients. Insulin-related overproduction of ET-1 could promote the atherogenic process and enhance the vascular tone to a greater extent in NIDDM than in nondiabetic patients with CAOD of the lower limbs.

Raised plasma endothelin-1 concentrations in patients with primary hypercholesterolemia without evidence of atherosclerosis.

The present study was designed to investigate the pattern of circulating endothelin-1 (ET-1), a potent vasoconstricting mitogenic endothelium-derived peptide, in relation to primary increase in serum cholesterol in humans. We measured plasma ET-1 concentrations by radioimmunoassay (Amersham, UK) in 8 patients (6 females and 2 males, aged 42-62 years) with primary hypercholesterolemia, non-smokers, without evidence of cardiovascular disease, and in 8 healthy sex-and age-matched control subjects. The mean (+/- SD) values of serum total cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol and triglycerides in the hypercholesterolemic subjects were 7.2 +/- 1.1 mmol/L, 5.1 +/- 1.1 mmol/L, 1.0 +/- 0.1 mmol/L and 2.4 +/- 0.9 mmol/L, respectively. The lipid profile of the controls showed a total cholesterol of 4.6 +/- 0.3 mmol/L, LDL cholesterol of 3.0 +/- 0.2 mmol/L, HDL cholesterol of 1.0 +/- 0.1 mmol/L and triglycerides of 1.2 +/- 0.2 mmol/L. The mean ET-1 plasma levels in the hypercholesterolemic patients were significantly higher than in the controls (4.2 +/- 0.1 pmol/L and 2.2 +/- 0.7 pmol/L, respectively, p < 0.001). Our data of raised circulating ET-1 in hypercholesterolemic patients without evidence of atherosclerosis suggest that an exaggerated release of ET-1 could contribute: 1) to impair endothelium-dependent vasodilation; 2) to promote the atherogenic process in hypercholesterolemia. Finally, it could represent a marker for hypercholesterolemic endothelial damage.

Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb.

BACKGROUND: Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm. METHODS: To investigate the endothelin-1 release in response to dynamic exercise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2 +/- 8.1 years) with peripheral arterial occlusive disease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital vein, at the onset of claudication pain, and 10 minutes after exercise. RESULTS: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001). CONCLUSIONS: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.

Atrial natriuretic peptide response to postural changes and upright exercise in patients with venous valvular insufficiency.

To investigate the effects of postural changes and upright exercise on atrial natriuretic peptide release and renin-angiotensin-aldosterone system behavior in patients with venous valvular insufficiency, plasma ANP, plasma renin activity and aldosterone were measured in 11 patients with venous disease and in 11 age-matched controls. In patients with large varicose veins and venous valvular dysfunction, standing was associated with a greater fall in circulating ANP levels (p < 0.05) and upright exercise was accompanied by a smaller rise in ANP concentrations (p < 0.05) as compared with controls. A significant (p < 0.001) inverse relationship was found between the number of venous segments with reflux and both upright and exercise plasma ANP concentrations (r = -0.91; r = -0.84, respectively). In the two groups the response of the renin-angiotensin-aldosterone system to upright position and physical stress was similar. These results suggest that a decreased atrial stretch, due to a reduced venous return, could account for the blunted ANP response to erect posture and exercise in patients with venous valvular incompetency.